MEDICAL
VON HOFFMANN
ACCESSION
THE
PHYSIOLOGY OF REPRODUCTION
THE PHYSIOLOGY OF
REPRODUCTION —
BY
FRANCIS H. A. JVJARSHALL
M.A. (CANTAB.), D.Sc. (EoiN.)
FELLOW OF CHRIST'S COLLEGE, CAMBRIDGE, AND UNIVERSITY LECTURER
IN AGRICULTURAL PHYSIOLOGY
WITH A PREFACE BY
PROFESSOR E. A. SCHAFER, Sc.D., LL.D., F.R.S.
AND CONTRIBUTIONS BY
WILLIAM CRAMER, PH.D., D.Sc.
AND
JAMES LOCHHEAD, M.A., M.D., B.Sc., F.R.C.S.E.
WITH ILLUSTRATIONS
LONGMANS, GREEN AND CO.
39 PATERNOSTER ROW, LONDON
NEW YORK, BOMBAY, AND CALCUTTA
1910
K
All rights reserved
M 33-
\9lft
TO
WALTER HEAPE, ESQ., M.A., F.R.S.
1767
PREFACE
THIS is the first time that the Physiology of the Organs
of Reproduction has been presented in a complete form,
and many who desire to obtain more precise knowledge
regarding the problems with which it deals, than is to be
found in text-books of Physiology, will welcome the
appearance of Dr. Marshall's book. The importance of
such knowledge to the community in general is now
becoming recognised, and the interest which the subject
awakens is no longer confined to members of the medical
profession and to breeders of animals. Especially will
the work furnish a much needed introduction to the
science of Eugenics, whilst the multiplicity of facts which
are set forth, and the manner in which questions of
difficulty are discussed, will have the effect at once of
satisfying and of stimulating inquiry in a most important,
if hitherto somewhat neglected, branch of Physiology.
E. A. SCHAFER.
UNIVEKSITY, EDINBURGH,
June 1910.
vii
CONTENTS
PAGE
INTRODUCTION . .... . . . .
CHAPTER I
THE BREEDING SEASON . . . . . . . . 4
Protozoa — Ccelenterata — Nemertea, &c. — Annelida — Arthropoda
— Mollusca — Echinodermata — Cephalochordata — Pisces —
Amphibia — Reptilia — Aves — Mammalia — Periodicity of
Breeding, &c.
CHAPTER II
THE (ESTROUS CYCLE IN THE MAMMALIA 35
Monotremata — Marsupialia — Rodentia — Ungulata — Cetacea —
Carnivora — Insectivora — Cheiroptera — Primates.
CHAPTER III
THE CHANGES THAT OCCUR IN THE NON-PREGNANT UTERUS DURING
THE CESTR.US CYCLE 75
The Cycle in Man — Monkeys — Lemurs — Insectivora — Carnivores
— Ungulates.
CHAPTER IV
CHANGES IN THE OVARY OOGENESIS GROWTH OF FOLLICLES
OVULATION FORMATION OF CORP RA LUTEA AND ATRETIC
FOLLICLES THE SIGNIFICANCE OF THE PROCESTROUS CHANGES
IN THE UTERUS . . . . . . . . .113
Dev lopment of Ovary and Oogenesis — Maturation and Ovulation
— The Formation of the Corpus Luteum — The Atretic Follicle
— Superf oetation — Formation of Ova — The Significance of the
Procestrous Changes.
CHAPTER V
SPERMATOGENESIS INSEMINATION 165
Structure of Spermatozoa — Seminal Fluid — Movements of Sper-
matozoa— Insemination.
ix
x CONTENTS
CHAPTER VI
PAGE
FERTILISATION 187
The Hereditary Effects of Fertilisation — Telegony — On Gametic
Selection and the Conditions Favourable for the Occurrence of
Fertilisation — Conjugation in the Protozoa — The Supposed
Chemotactic Properties of Spermatozoa and their Relation
to the Phenomena of Fertilisation — Artificial Aids to Fertilisa-
tion— Artificial Parthenogenesis.
CHAPTER VII
THE ACCESSORY REPRODUCTIVE ORGANS OF THE MALE AND THE
MECHANISMS CONCERNED IN INSEMINATION .... 227
The Vesiculse Seminales — The Prostate Gland — -Cowper's Glands
—The Copulatory Organ — The Mechanisms of Erection,
Ejaculation, and Retraction.
CHAPTER VIII
THE BIOCHEMISTRY OF THE SEXUAL ORGANS 263
The Female Generative Organs : Mammals, Birds, Invertebrates
— The Male Generative Organs : The Semen — The Chemistry
of the Spermatozoon.
CHAPTER IX
THE TESTICLE AND THE OVARY AS ORGANS OF INTERNAL SECRETION . 303
The Correlation between the Testis and the other Male Organs and
Characters — The Correlation between the Ovary and the other
Female Organs and Characters — The Factors which determine
the Occurrence of Heat and Menstruation — The Function of
the Corpus Luteum — The Supposed Internal Secretion of the
Uterus — The Correlation between the Generative Organs and
the Ductless Glands — General Conclusions regarding the
Internal Secretions of the Ovary and the Testis — The Effects
of Castration upon the General Metabolism.
CHAPTER X
FOETAL NUTRITION : THE PLACENTA . . . . . . .357
Part I. The Placenta as an Organ of Nutrition — i. Historical
Survey — ii. Structure and Functions of the Epithelial In-
vestment of the Villi — iii. The Decidua.
Part II. The First Stages of Pregnancy : Placental Classification
— i. The Ovarian Ovum.— ii. The Fertilised Ovum and its
Coverings. — iii. The Uterine Mucosa. — iv. Placental Classi-
fication.
Part III. The Fretal Membranes, the Yolk-sac, and the Placenta
— i. General Anatomy of the Foetal Membranes. —ii. The Nutri-
tive Importance of the Yolk-sac (Marsupialia, Ungulata,
Carnivora, Proboscidea and Hyrax, Rodentia, Insectivora,
CONTENTS xi
PAGE
Primates). — iii. The Placenta in Indeciduata (Ungulata,
Lemuroidea, Cetacea, Edentata, and Sirenia).— iv. The
Placenta in Deciduata ( Garni vora, Proboscidea, Hyrax,
Rodentia, Insectivora, Cheiroptera, Primates). — v. General -
Considerations of Foetal Nutrition and the Placenta : A. The
Plan of Placental Formation. B. The Nature of the Tropho-
blastic Activity.
CHAPTER XI
THE CHANGES IN THE MATERNAL ORGANISM DURING PREGNANCY . 490
I. The Stimulus for the Maternal Changes during Pregnancy. —
II. Change in the Metabolism of the Mother during Pregnancy :
A. The Source of the Materials transferred to the New Or-
ganism. B. The Body-Weight during Pregnancy. C. The
Protein Metabolism in Pregnancy. D. The Carbohydrate
Metabolism in Pregnancy. Ji.1. The Metabolism of Fats in
Pregnancy. F. The Metabolism of Metals and Salts in
Pregnancy. (?. Respiratory Exchange during Pregnancy. —
III. The Changes in the Maternal Tissues during Pregnancy.
CHAPTER XII
THE INNERVATION OF THE FEMALE GENERATIVE ORGANS UTERINE
CONTRACTION PARTURITION THE PUERPERAL STATE . . 525
The Innervation of the External Generative Organs — The Inner -
vation of the Ovaries — The Innervation of the Uterus and
Vagina and the Mechanism of Uterine Contraction — The
Normal Course of Parturition in the Human Female —
Parturition in other Mammalia — The Nervous Mechanism of
Parturition — Changes in the Maternal Organism — The Cause
of Birth — Prolonged Gestation — The Puerperium.
CHAPTER XIII
LACTATION . . . . . . . . ... 553
Structure of the Mammary Glands — The Composition and Pro-
perties of Milk — The Influence of Diet and other Factors on
the Composition and Yield of Milk — The Duration of Lacta-
tion— The Discharge of Milk — The Formation of the Organic
Constituents of Milk — The Normal Growth of the Mammary
Glands — The Factors which are concerned in the Process of
Mammary Growth — The Factors which are concerned in the
Commencement of Mammary Secretion — Criticisms.
CHAPTER XIV
FERTILITY ........... 586
Effect of Age — Effects of Environment and Nutrition — Effect of
Prolonged Lactation — Effect of Drugs — Effects of In-Breed-
ing and Cross -Breeding — Inheritance of Fertility — Certain
Causes of Sterility — Artificial Insemination as a Means of
overcoming Sterility — Abortion — The Increase of Fertility,
a Problem of Practical Breeding — The Birth-Rate in Man.
xii CONTENTS
CHAPTER XV
PAGE
THE FACTORS WHICH DETERMINE SEX 623
i. Theories which assume that Sex-determination takes place
subsequently to Fertilisation. — ii. Theories which assume that
Sex-determination takes place at the time of Fertilisation or
previously to Fertilisation. — lii. Theories which limit Sex-
determination to no particular period of development, or
which assert that Sex may be established at different periods —
Hermaphroditism and Sexual Latency — General Conclusions.
CHAPTER XVI
PHASES IN THE LIFE OF THE INDIVIDUAL THE DURATION OF LIFE
AND THE CAUSE CF DEATH 659
Growth of the Body before Birth — Growth of the Body after
Birth — Puberty — The Menopause — Senescence — The Duration
of Life and the Cause of Death.
INDEX . . . 689
ILLUSTRATIONS
FIG. PAGE
1. Diagram illustrating the " Wellenbewegung " hypothesis . 67
2. Transverse section through Fallopian tube showing folded
epithelium and muscular coat . . . . . .76
3. Seition of a cornu of a rabbit's uterus ..... 77
4. Cross-section through cervical canal of human uterus . . 78
5. Section through wall of vagina of monkey (upper part) . 79
6. Section through wall of vagina of monkey (lower part) . . 81
7. Se tion through mucosa of human uterus showing pre-menstrual
congestion 82
8. Section through mucosa of human uterus showing extravasation
of blood 84
9. Section through mucosa of human uterus showing sub -epithelial
hsematomata ......... 86
10. Section through mucosa of human uterus showing bleeding into
the cavity during menstruation . . . . .87
11. Section through mucosa of human uterus during the recupera-
tion stage .......... 88
12. 13. Sections through prooestrous uterine mucosa of dog . 100-101
14. Section through edge of mucosa of dog during an early stage
of recuperation ......... 103
15. Section through portion of mucosa of dog during recuperation
period 104
16. Section through portion of mucosa of dog during lats stage of
recuperation ......... 105
17. Section through portion of prooestrous uterine mucosa of rabbit
showing glandular activity . . . . . .106
18. Section through portion of uterine mucosa of sheep, showing
black pigment formed from extravasated blood . .109
19. Section through ovary of cat . . . . . . .114
20. Section through ovary of adult dog . . . . .115
21. Section through ovary of pig embryo 116
22. Cortex of pig embryo showing germinal epithelium, &c. . .117
23. Various stages in the development of the Graafian follicle
(rabbit) 119
xiii
xiv ILLUSTRATIONS
FIG. PAGE
24 to 27. Developing ova from ovary ..... 120-121
28. Ovary at birth, showing primordial follicles .... 123
29. Young oocyte 126
30. Young human Graafian follicle . . . . . .127
31. Human ovum at termination of growth period . . . 128
32. Human ovum examined fresh in the liquor folliculi . . .129
33. Recently ruptured follicle of mouse . . . . . .144
34. Early stage in formation of corpus luteum of mouse . .145
35. Late stage in formation of corpus luteum of mouse . . .146
36. Corpus luteum of mouse fully formed . . . . 147
37. Section through old corpus luteum ...... 153
38. Section through follicle in early stage of degeneration . .155
39. Section through follicle in late stage ..... 157
40. Section through human testis and epididymis . . . .166
41. Section through testis of monkey 167
42. Section through portion of two seminiferous tubules in testis
of rat 169
43. A cell of Sertoli with which the spermatids are beginning to be
connected (human) 170
44. Diagram illustrating the cycle of phases in spermatogenesis . ib.
45. Scheme of spermatogenesis and oogenesis . . . . .171
46. Human spermatozoa on the flat and in profile . . . .173
47. Human Spermatozoa . . . . . . . .174
48. Different forms of spermatozoa from different species of
animals .......... 175
49. Diagram illustrating wave-like movement of swimming sperma-
tozoon .......... 177
50. Successive stages in the fertilisation of an ovum of Echinus
esculentus, showing the entrance of the spermatozoon . 188
51. Three stages in the conjugation of male and female nucleus
(Echinus) 189
52. Fertilisation process in bat's ovum . . . . . .190
53. Passage of convoluted seminiferous tubules into straight
tubules, &c 228
54. Transverse section through the tube of the epididymis . . 229
55. Transverse section through commencement of vas deferens . 230
56. Section through part of human prostate ..... 235
57. Section through prostate gland of monkey . 237
58. Transverse section through adult human penis . . . 243
59. Section through erectile tissue ..... . 244
60. Part of transverse section through penis of monkey . . . 245
61. Distal end of ram's penis, showing glans and filiform appendage 247
62. Transverse section through filiform appendage of ram . . 248
ILLUSTRATIONS xv
FIG. PAGE
63. Transverse section through middle of glans penis of ram . . 249
64. Distal end of bull's penis showing glans, &c. .... 250
65. End-bulb in prostate . . ._ 259
66. Diagram illustrating inner vation of genital organs of male cat . 261
67. Transverse section through rabbit's uterus after ovariotomy . 318
68. Transverse section through bitch's uterus 9£ months after
ovariotomy ......... 319
69. Section through ovary of rat after transplantation on to peri-
toneum 321
70. Section through ovary of rat after transplantat on on to peri-
toneum .......... 322
71. Transverse section through normal uterus of rat . . . 323
72. Transverse section through uterus of rat after ovariotomy . 324
73. Transverse section through uterus after ovarian transplantation 325
74. Section through rat's kidney into the tissue of which an ovary
had been transplanted . . . . . .327
75. Part of an early human chorionic villus . . . . .362
76. Early blastocyst of rabbit 372
77. Diagram to illustrate the three parts of the wall of the yolk-
sac (rabbit) 381
78. Diagram of an opossum embryo and its appendages . . 382
79. Diagram showing the arrangement of foetal membranes in
Dasyurus 383
80. Diagram showing the arrangement of foetal membranes in
Perameles 385
81. Elongated blastocyst of sheep at thirteenth day of pregnancy 386
82. Transverse section through blastocyst of sheep at twenty-
fifth day . 387
83. Blastodermic vesicle of rabbit ....... 388
84. Diagram of blastodermic vesicle of rabbit in longitudinal
section .......... 389
85. Diagram to illustrate foetal membranes of Erinaceus . .391
86. Hypothetical section of human ovum imbedded in decidua . 393
87 Portion of injected chorion of pig 394
88. Section through wall of uterus and blastocyst of pig at twentieth
day of pregnancy ........ 395
89. Diagram representing a stage in the formation of the placenta
(pig) ... .396
90. Section through uterine and embryonic parts of a cotyledon of
sheep at twentieth day of pregnancy . . . .398
91. Section through base of foetal villus, &c. (sheep) . . .399
92. Columnar trophoblast -cells from the base of foetal villus at
third month of pregnancy (cow) to show phagocytosis . 401
xvi ILLUSTRATIONS
FIG. PAGE
93. First stage of cellular secretion in placenta of cow . . . 405
94. Ingestion and disintegration of red blood corpuscles by tropho-
blast of sheep ......... 408
95. Absorption of " Stabchen " by trophoblast of sheep . . 409
96. The uterine mucosa of dog at about twenty-third day of
pregnancy 412
97. Ovum with zonary band of villi . . . . . .413
98. The angioplasmode of dog at thirtieth day of pregnancy . .415
99. The labyrinth and green border of placenta of dog at fortieth
day of pregnancy ........ 417
100. Transverse section of a four days' gestation sac of rabbit . 421
101. Transverse section of a seven days' gestation sac of rabbit . 422
102. Thickened ectoderm in rabbit, attached to placental lobe . . 424
103. Iron granules in placenta of rabbit at eighteenth day of
pregnancy ......... 429
104. Glycogenic areas of rabbit's placenta at twelfth day of
pregnancy ......... 432
105. Inversion of germinal layers in blastodermic vesicle of mouse . 438
106. Longitudinal sections of implantation cavity of field-mouse
about eighth day of pregnancy . . . . . .440
107. Longitudinal section of uterus and implantation cavity of
guinea-pig . . . . . . . . 443
108. Blastodermic vesicle of guinea-pig showing inversion of ger-
minal layers ......... 444
109. Implantation cavity of guinea-pig . . . . . . 445
110. Implantation cavity of guinea-pig ...... 446
111. Allantoidean diplo-trophoblast of Erinaceus .... 448
112. Section in situ of ovum of Erinaceus ..... 450
1 13. The extension of yolk-sac against lacunar trophoblast in
Erinaceus 451
114. Transverse section through uterus of Sorex at a stage when
the blastocysts are still in the oviducts . . . .452
1 15. Part of the anto-mesometrial wall of the uterus of Sorex . . 453
116. Uterus and embryo of Sorex ....... 455
117. Orifice of uterine gland of mole with trophoblastic dome . . 457
118. Replacement of omphaloidean by allantoidean placenta . . 459
119. Placenta of bat 461
120. Median longitudinal section of an early human ovum, 0-4 mm.
in length 464
121. Diagram of the earliest human ovum hitherto described . . 468
122. Section through the wall of the uterus in the early part of
pregnancy ......... 469
123. Section of a portion of the wall of the human blastocyst . . 470
ILLUSTRATIONS xvii
,,„;. PAGE
124. Section of a portion of the necrotic zone of the decidua, &c. . 471
1 25. Section through embryonic region of ovum .... 472
126. Condition of the glands at the beginning of pregnancy in Man 473
127. Median longitudinal section of embryo of 2 mm. . . . 475
128. Diagram of stage in development of human placenta . 476"
129. Fat in a villus of human placenta 479
130. Iron granules in a villus of the placenta in Man . . . 480
131. The first stage in the revolution of the equine foetus . . 535
132. The foal in the normal position for delivery ... . . 536
133. Virginal external os (human) ...>.... 550
134. Parous external os (human) .... ib.
135. Section of mammary gland of woman ..... 556
136. Section of mammary gland (human) during lactation . . 557
137. Section of mammary gland (human) in full activity . . . 558
13S. Section through an alveolus with fat drops in cells . . . 559
139. Section of developing mammary gland of horse . . . 574
140. Section of mammary gland (human) showing developing
alveoli .......... 575
141 to 147. Diagrams from Minot's Problem of Age, Growth,
and Death 663-9
148. Section through ovary of woman of fifty-six showing degenera-
tion of follicles, &c 673
149. Section through uterine mucous membrane of woman of sixty . 674
150. Section through vaginal mucous membrane of woman of
sixty-one . . . . . . . . . . 675
151. Group of nerve cells from the first cervical ganglion of a child at
birth 677
152. Group of nerve cells from the first Cervical ganglion of a man
of ninety -two ......... 678
153. Land tortoise aged at least eighty-six belonging to M. Elie
Metchnikoff 680
154. Lonk sheep aged eighteen years, with her last lamb . . .681
ERRATA
P. 51, footnote1, instead of " prjewalsky" read " prjewalskii."
P. 306, 1. 12, instead of "castration.2" read "castration.1"
(that is, see footnote x instead of footnote 2).
P. 306, 1. 13, instead of "about horned cattle" read "about
many horned cattle."
P. 306, 1. 9 from bottom, instead of " males.1 " read " males.2 "
(that is, see footnote 2 instead of footnote 1).
P. 316, 1. 16, before " Ruticilla" read "a specimen of."
P. 355, 1. 3 from bottom, instead of " Priestley" read " Pembrey."
THE
PHYSIOLOGY OF REPRODUCTION
INTRODUCTION
SINCE the time when physiology first became an organised science
many volumes have been written on the digestive, excretory,
nervous, and other systems of the body, but no attempt has
yet been made to supply those interested in the reproductive
processes with a comprehensive treatise dealing with this branch
of knowledge. Indeed, in most text-books on physiology now
commonly in use either the section devoted to the reproductive
organs is restricted to a few final pages seldom free from
error, or else the subject is entirely omitted. Yet generative
physiology forms the basis of gynaecological science, and must
ever bear a close relation to the study of animal breeding. In
writing the present volume, therefore, I have been actuated by
the desire to supply what appears to me to be a real deficiency ;
and in doing so I have attempted, however inadequately, to
co-ordinate or give a connected account of various groups of
ascertained facts which hitherto have not been brought into
relation. For this purpose I have had occasion to refer to many
books and memoirs dealing with subjects that at first sight might
have been supposed to differ considerably. Thus, works on
zoology and anatomy, obstetrics and gynaecology, physiology and
agriculture, anthropology and statistics, have been consulted
for such observations and records as seemed to have a bearing
on the problems of reproduction.
My sources of information are duly acknowledged in the
footnotes, but I am glad to take this opportunity of mentioning
the following works from which I have obtained special help :
" The Evolution of Sex," by Professors Geddes and Thomson,
" Obstetrics/' by Professor Whitridge Williams, the sections on
A
2 THE PHYSIOLOGY OF REPRODUCTION
the male and female reproductive organs, by Professor Nagel
and Dr. Sellheim, in Professor Nagel's " Handbuch der Physi-
ologic des Menchen," " Experimental Zoology/3 by Professor
T. H. Morgan, and the writings of Mr. Walter Heape.
The present volume is addressed primarily to the trained
biologist, but it is hoped that it may be of interest also to
medical men engaged in gynaecological practice, as well as to
veterinarians and breeders of animals. As a general rule, I
have confined myself to the physiology of generation among
the higher forms, and more particularly the Mammalia, but
I have not hesitated to discuss the reproductive processes
in the Invertebrata in cases where they seemed likely to
elucidate the more complex phenomena displayed by the
higher animals. The all-important questions of heredity and
variation, although intimately connected with the study of re-
production, are not here touched upon, excepting for the merest
reference, since these subjects have been dealt with in various
recent works, and any attempt to include them would have
involved the writing of a far larger book. Similarly, the sub-
ject matter of cytology, as treated in such works as Professor
Wilson's volume on the cell, is also for the most part excluded.
It may be objected that, for a book on physiology, too much
space is devoted to the morphological side of the subject. This
has been done purposely, since it seemed impossible to deal
adequately with the physiological significance of the various
sexual processes without describing the anatomical changes
which these processes involve.
In preparing this work I have been assisted by many
friends. I have been fortunate in securing the co-operation
of Dr. William Cramer and Dr. James Lochhead, of the
University of Edinburgh. Dr. Cramer has contributed the
section on the biochemistry of the sexual organs, while Dr.
Lochhead has written the chapters on foetal nutrition and the
metabolism of pregnancy, a labour of no inconsiderable magni-
tude in view of the complexity of the subject. I take this
opportunity of recording my indebtedness to Mr. Walter Heape,
through whose influence I was first led to realise the importance
of generative physiology both in its purely scientific and in its
practical aspects. I am under no light obligation to Professor
INTRODUCTION 3
Schafer for valuable and ready help at all stages in the prepara-
tion of this volume. Professor Schafer has kindly looked through
the manuscript of the chapter on " The Testicle and Ovary as
Organs of Internal Secretion," besides giving helpful advice
and criticism on various points connected with publication.
Indeed, it is not too much to say that had it not been for him,
the book would scarcely have been written. Dr. H. K. Anderson
and Professor Sutherland Simpson have read the manuscript
or proofs of the chapter dealing with " The Accessory Male
Organs." Mr. E. S. Carmichael, of the Royal Infirmary, Edin-
burgh, has read the section dealing with parturition. Dr. J. H.
Ashworth has looked through the chapter on " Fertilisation " ;
and Dr. F. Gr. Hopkins has done the same for Dr. Cramer's
biochemical chapter. Dr. Anderson and Dr. Ashworth have
also given me the benefit of their special knowledge in other
parts of the work. To all these I am under obligations. I
wish also to tender my thanks to those authors and publishers
who have kindly allowed me to reproduce illustrations from their
respective works, as well as to record my indebtedness to the
following, who have been of service by giving me information,
important references, or assistance in other ways : — Dr. Nelson
Annandale, Superintendent of the Indian Museum, Calcutta,
Dr. W. Blair Bell, of Liverpool, Mr. Eagle Clarke, Super-
intendent of the Scottish National Museum, Professor J. C.
Ewart, of the University of Edinburgh, Professor J. P. Hill, of
University College, London, Dr. A. C. Haddon, of Christ's
College, Dr. W. A. Jolly, of the University of Edinburgh,
Dr. Janet E. Lane-Claypon, of London, Mr. D. Gr. Lillie, of St.
John's College, Mr. K. J. J. Mackenzie, of Christ's College, Mr.
F. A. Potts, of Trinity Hall, Dr. C. G. Seligmann, of London,
and Mr. A. E. Shipley, of Christ's College. Lastly, I wish to
acknowledge the assistance of Mr. C. H. Crawshaw, of Christ's
College, in the correction of the proofs, as well as to express
my obligations to Mrs. Kingston Quiggin for the willing labour
she has expended in preparing the index and finally revising
the text, and to Mr. Richard Muir for the skilful manner in
which he has executed those drawings which are new.
CHAPTER I
THE BKEEDING SEASON
" To everything there is a season, and a time to every purpose under the
heaven." — Ecclesiastcs iii. 1.
" IT is well known that almost all animals, except Man, have a
stated season for the propagation of their species. Thus the
female cat receives the male in September, January, and May.
The she- wolf and fox in January ; the doe in September and
October. The spring and summer are the seasons appointed
for the amours of birds, and many species of fishes. The
immense tribe of insects have likewise a determinate time for
perpetuating their kind ; this is the fine part of the year, and
particularly in autumn and spring. The last-mentioned class
of beings is subject to a variation that is not observed in the
others. Unusual warmth or cold does not retard or forward
the conjunction of birds or quadrupeds ; but a late spring
delays the amours of insects, and an early one forwards them.
Thus it is observed that, in the same country, the insects on
the mountains are later than in the plains."
The foregoing quotation from Spallanzani's "Dissertations," 1
although not strictly accurate in all its statements, contains
a clear recognition of two fundamental facts which indeed have
been realised from the earliest times ; firstly, that the periods
of reproductive activity among the great majority of animals
(not to mention plants) occur rhythmically, the rhythm having a
close connection with the changes of the seasons ; and secondly,
that the reproductive rhythm is liable, to a greater or less
extent, to be disturbed or altered by climatic or other environ-
mental influences. And while there may be a basis of truth
for the statement that the periodicity of the breeding season
1 Spallanzani, Dissertations relative to the Natural History of Animals and
Vegetables. Translated from the Italian, vol. ii., London, 1784.
THE BREEDING SEASON 5
in the higher animals is less liable to modification than is the
case with certain of the lower forms of life, there is abundant
evidence that among the former no less than among inseets -
the sexual functions are affected by external conditions and
food supply.
Darwin remarks that any sort of change in the habits of life
of an animal, provided it be great enough, tends in some way to
affect the powers of reproduction, " The result depends more
on the constitution of the species than on the nature of the
change ; for certain whole groups are affected more than others ;
but exceptions always occur, for some species in the most fertile
groups refuse to breed, and some in the most sterile groups
breed freely." " Sufficient evidence has now been advanced
to prove that animals when first confined are eminently
liable to suffer in their reproductive systems. We feel at first
naturally inclined to attribute the result to loss of health, or at
least to loss of vigour ; but this view can hardly be admitted
when we reflect how healthy, long-lived, and vigorous many
animals are under captivity, such as parrots and hawks when
used for hunting, chetahs when used for hunting, and elephants.
The reproductive organs themselves are not diseased ; and the
diseases, from which animals in menageries usually perish, are
not those which in any way affect their fertility." x
It would seem probable that failure to breed among animals
in a strange environment is due not, as has been suggested, to
any toxic influence on the organs of generation, but to the
same causes as those which restrict breeding in a state of nature
to certain particular seasons, and that the sexual instinct can
only be called into play in response to definite stimuli, the
existence of which depends to a large extent upon appropriate
seasonal and climatic changes.2
There are at present no sufficient data for a comparative
account of the physiology of breeding among the lower animals ;
and in the present chapter, which is preliminary in character,
I shall content myself with stating a few general facts about
1 Darwin, Variation of Animals and Plants, Popular Edition, vol. ii.,
London, 1905.
2 See especially page 20, where Bles's observations on the breeding .habits
of Amphibia are referred to.
6 THE PHYSIOLOGY OF REPRODUCTION
the breeding season, giving illustrations, taken from various
groups of Vertebrates and Invertebrates, of its seasonal re-
currence, and the manner in which this varies under altered
conditions of life.
PROTOZOA
Among the Protozoa the organisms pass through successive
phases of vitality, which are comparable to the different age-
periods of the Metazoa. In such simple forms of life, fission or
division into two parts is the usual method of reproduction,1
and the frequency of its occurrence appears to depend more
upon the phase which has been reached in the life-cycle, than
upon the influences of the environment. Thus, there is a
period of extreme vigour of cell-multiplication, corresponding
to the youth of a metazoon ; secondly, there is a period of
maturity, characterised by changes in the chemical and physical
properties of the cell, and leading to the formation of con-
jugating individuals ; and finally, in forms which do not con-
jugate, there is a period of senescence which ends in death.
It is interesting to note, however, that the rapidity of fission
is affected by the temperature and the food ; for example, an
individual of the Ciliate Infusiorian, Stylonychia pustulata, if
well supplied with food, divides once in twenty-four hours in
a temperature of from 5° to 10° C., and once in twelve hours
in a temperature of from 10° to 15° C.2 Again, Flagellate
Infusoria of different kinds have been induced to conjugate by
changing the temperature or increasing the density in the
surrounding medium.3 Furthermore, the life-cycle of Para-
moBcium may be renewed without the occurrence of conjuga-
tion, that is to say, fission can be made to continue and
senescence can be avoided, by introducing a change in the
1 In this process no material is lost, and two simple nucleated organisms
result. During the period of maturity referred to in the text, multiplication
is often preceded by union (either temporary or complete) of two individuals,
and this process is called conjugation (see p. 211, Chap. VI.).
2 Sedgwick, Student's Text-Book of Zoology, vol. i., London, 1898.
3 Calkins points out that the same experiment is performed by mosquitoes
and other insects on certain parasitic Protozoa, as when a parasite is with-
drawn from the hot environment of the Mammalian blood into the compara-
tively cold region of the mosquito's alimentary tract. (" The Protozoan
Life-Cycle," Biol. Bull, vol. xi., 1906.)
THE BREEDING SEASON 7
composition of the medium surrounding the culture.1 (See
p. 213.)
Moreover, there is evidence that in the case of Colpoda
steini at least the occurrence of conjugation is determined
entirely by the conditions of the surrounding medium.
CCELENTERATA
With the majority of the Metazoa, as already indicated,
there is a more or less definitely restricted season to which the
occurrence of the chief reproductive processes is confined.
Thus in the common hydra of Bengal (Hydra orientalis,
Annandale), which, like most other Ccelenterates, reproduces
by budding as well as by the sexual method,2 the former process
occurs chiefly during winter, the buds developing into new
individuals. Towards the beginning of the hot weather budding
becomes less active, and in some individuals ceases altogether,
while the same thing happens during periods of temporary
warmth in winter. A rise in temperature induces a proportion
of the individuals present in an aquarium or pond to develop
testes or male reproductive glands ; if the rise is considerable
it may cause a few of the remaining individuals to produce ova.
On the other hand, no individual living in its natural environ-
ment has been known to exhibit any sign of sex after the rise
in temperature had become steady. The conditions most
favourable to the production of ova appear to be a period of
comparatively low temperature and abundant nutrition fol-
lowed by a sudden but not excessive rise of temperature.3
1 Calkins, loc. cit.
« 2 Asexual reproduction is of very common occurrence among the majority
of the lower animals and plants. It may take the form of simple binary
fission (in unicellular organisms), of spore formation, or of germination or
budding. Sexual reproduction consists essentially of the union of two cells
and their subsequent division to give rise to the new individual. In the
multicellular organisms (Metazoa and Metaphyta) there are two kinds of con-
jugating cells, or gametes, which are specialised for the purpose. These are
produced by the male and female respectively, and are known as spermatozoa
and ova. Thus, sexual reproduction in the Metazoa is a modification of con-
jugation in the Protozoa. (See Chap. VI.)
3 Annandale, " The Common Hydra of Bengal," Memoirs of the Asiatic
Society of Bengal, vol. i., 1906. Of. Whitney, " The Influence of External
Factors in causing the Development of the Sexual Organs in Hydra viridis,"
8 THE PHYSIOLOGY OF REPRODUCTION
Some of the marine hydroids show an alternation of genera-
tions which does not appear at first sight to be in any way
related to change in the environment. In such cases the
fertilised ovum develops into a polyp which gives rise to a
colony of polyps by a process of sexual reproduction. After
the colony has reached a certain size, a new kind of bud is
formed, and this becomes a jelly-fish. The latter, after leading
an independent existence, produces eggs, and these in turn
become fertilised, giving rise to a new generation of polyps.
Morgan points out that as the polyp colony goes on increasing
in size, its relation to its surroundings must undergo change,
and that, very possibly, it is this change which determines the
development of jelly-fish in place of polyps. If this inter-
pretation is correct the breeding season among marine hydroids
is controlled by environmental conditions, just as it is among
most other animals.1
Some interesting observations have been recorded by
Ash worth and Annandale 2 about the breeding habits of sea-
anemones. The species Sagartia troglodytes and Actinia mesem-
bryanthemum, which are very prolific in captivity, have been
noticed to breed regularly in the early spring. Actinia com-
mences to produce young in the beginning of February, and
Sagartia about a month later. As a rule the young are ex-
truded in the early morning, and one individual may repeat
Arch. f. Entwick.-Mechanik, vol. xxiv., 1907. Whitney says that in Hydra
viridis an abundance of food following a low temperature causes a suppression
of the formation of testes and ova.
1 Morgan, Experimental Zoology, New York, 1907. Morgan shows that
the same point is illustrated by certain recent experiments of Klebs on
flowering plants. These at first produce only leaves and branches. When
they reach a certain size they produce flowers. Klebs regards the develop-
ment of the flowers as beiug due to a relation that becomes established
between the plant (when it has reached a certain stage of growth) and the
environment. He shows also that by altering the environment a shoot may
be induced to go on growing vegetatively, when it would ordinarily develop
into a flowering branch. The flowering of the plant, therefore, is not merely
the culmination of its form, as most botanists regard it. For much valuable
and suggestive information on the factors which control breeding in plants
G. Klebs' work should be consulted. ( Willkilrliche Entwickelungsanderungcn bei
Pflanzen, 1903.)
2 Ashworth and Annandale, "Observations on some Aged Specimens of
Sagartia troglodytes, and on the Duration of Life in Ccelenterates," Proc. Roy.
Soc. Edin., vol. xxv., 1904.
THE BREEDING SEASON 9
the process every morning for a number of weeks, when the
breeding season comes to an end. In one season, when the
aquaria were somewhat neglected, the specimens of Sagartia
produced fewer young than usual, and these were not extrudect
until the beginning of April. Specimens of Actinia living in
the same aquaria were more prolific, but their breeding season
was also somewhat retarded. In the month of August two
anemones of the species Sagartia troglodytes were brought from
Thorshavn in the Faroe's, and placed in the aquaria. In the
following October both of these produced several young ; while
in April of the next year one of them again gave birth, but only
to a single anemone. It seems probable that in this case the
change of temperature or environment had induced the anemones
to breed at an unusual season ; for it is unlikely that October
is the normal period for reproduction in the Faeroes, as by this
time the sea has already begun to run high, and there would be
a great risk of the young anemones becoming destroyed, being
unable to attach themselves.
Ashworth has pointed out 1 that in the coral Xenia hick-
soni, which lives in the tropics, there is every evidence that
spermatozoa are discharged over a very considerable period,
if not practically throughout the whole year, whereas in the
related form Alcyonium digitatum, of Northern Europe, the
period during which the spermatozoa are discharged is limited
to about a month in the winter. Ashworth remarks that the
difference is probably due to the fact that Xenia, living on
reefs in the shallow waters of tropical seas, is not subject to
great variations in temperature and food-supply, while with
Alcyonium., such variations are no doubt considerable. In a
similar way Miss Pratt,2 who has studied the process of oogenesis
in Sarcophytum, Holophytum, and Sclerophytum, concludes that
the sexually mature condition in these tropical genera extends
over a considerably longer period than in the case of corals
inhabiting temperate waters.
It may also be noted that, whereas in the Ctenophora of
the Mediterranean the breeding season extends throughout the
1 Ashworth, " Structure of Xenia hicksoni," Quar. Jour. Micr. Science,
vol. xlii.
2 Pratt, "On Some Alcyonidae," Herdman's Ceylon Reports, vol. iii.
10 THE PHYSIOLOGY OF REPRODUCTION
year, in members of the same class in northern seas it only
lasts through the summer.1
NEMERTEA, &c.
The breeding season and its relation to the environment
have formed the subject of a careful investigation by Child 2
in the case of a small Nemertean, Stychostemma asensoriatum,
which is found very abundantly in one of the park lagoons of
Chicago. The season extends from May to November or
December, according to the temperature of the water. Egg-
laying can occur freely in the laboratory, the eggs being de-
posited always during the night, or in darkness, when the animals
move about freely. Although breeding in the natural state is
restricted to the warmer part of the year, eggs can be obtained
in the laboratory at practically any time, by simply regulating
the temperature. Thus egg-laying can be induced in the winter
at ordinary room-temperature, even though the worms are kept
without food. " In animals which contained only a few small
oocytes when taken, and which are kept in clean water without
food, the growth of the oocytes will continue, and within a
week or two eggs may be laid/' " The body of the animal
may even decrease somewhat in size during the growth of the
oocytes." It is clear, therefore, that in Stychostemma the limits
of the breeding season are determined chiefly by the temperature
of the water, and that food is a factor of secondary importance.
Similarly, in. the case of the parasitic Trematode, Diplozoon
paradoxum, which ordinarily produces eggs only in the summer,
it has been found that the formation of eggs could be artificially
prolonged throughout the winter, if the fishes on whose gills
the animal lives are kept in an aquarium at summer heat.3
ANNELIDA
Certain species of Polychset Annelids, known as the Palolo
worms, exhibit a quite remarkable regularity in the periodicity
of their breeding habits. During their immaturity all the Palolos
1 Bourne, "The Ctenophora," Treatise on Zoology, vol. ii., London, 1900.
2 Child, " The Habits and Natural History of Stychostemma," American
Naturalist, vol. xxxv., 1901.
3 Semper, Animal Life, London, 1881.
THE BREEDING SEASON 11
live in burrows at the bottom of the water. With the attain-
ment of sexual maturity, and under certain peculiar conditions,
they swarm out for purposes of breeding. In the Atlantic
Palolo (Eunice fucata) and the South Pacific Palolo (Eunice
viridis) the process invariably takes place twice, upon or near
the day of the last quarter of the moon ; but with the former
species it occurs in June and July, and with the latter in October
and November. In the Japanese Palolo (Ceratocephale osawai)
the swarming takes place on nights closely following the new
and full moons (i.e. when the spring tides occur), in October
and November, the worms swimming out regularly four times
a year. Each swarming-period lasts from one to four days. It
has been noted further that the swarm is greater after the new
moon (when the spring tide is highest) than after the full moon
(when the tide is not so high), that each swarming takes place
invariably just after the flood in the evening, that it continues
for from one to two hours, and is generally larger on warm,
cloudy nights than on clear, chilly nights. It would appear also
that no individual worm takes part in more than one swarming
in the year.1
ARTHROPODA
Innumerable instances of the periodicity of breeding and its
relation to seasonal and environmental changes might be ad-
duced from the great group of Arthropods, but the reason for
the variations which occur is not always obvious. Thus, in the
common crayfish (Astacus fluviatilis), in France the males are
said to approach the females in November, December, and
January, whereas in England they begin to breed as early as
the commencement of October, if not earlier.2 Also, in the
Cape species of Peripatus (P. capensis) birth takes place in a
fixed season (during April and May), whereas, in the South
American species, births are said to occur probably throughout
the entire year.3
In the case of the hemipterous insect known as the plant-
louse (Aphis), we have evidence that the mode of reproduction
1 Izuka, " Observations on the Japanese Palolo/' Jour, of the College of
Science, University of Tokyo, vol. xvii., 1903.
2 Huxley, The Crayfish, London, 1880.
3 Sedgwick, " Peripatus," Camb. Nat. Hist., vol. xii., London, 1901.
12 THE PHYSIOLOGY OF REPRODUCTION
is dependent upon temperature. In a favourable summer the
females of this animal may produce as many as fourteen con-
secutive generations of young by parthenogenesis, the ova
undergoing development without being fertilised by the male.
At the beginning of the winter male plant-lice make their
appearance and fertilise the eggs, which develop in the succeeding
spring. Reaumur, however, by artificially maintaining a con-
stant summer temperature, succeeded in producing more than
fifty parthenogenetic generations of plant-lice, all descended
from a single mother.1
Morgan, however, describes some observations which seem
to indicate that the change is not merely due to temperature.
He shows, for example, that the sexual forms of Aphis may
appear in the autumn before the onset of the cold weather, and
conversely that many individuals may continue to reproduce
parthenogenetically, until finally they perish from the cold.
Morgan suggests that the alternation in the mode of reproduction
may depend upon changes which take place in the food-plant
in the autumn, instead of being solely a temperature effect.
He shows also that there is evidence for the conclusion that in
the genus Chermes, in which the alternation of generations
occurs between the fir-tree and the larch, the conditions existing
on the larch are those that call forth the sexual forms.2
It has been supposed that the change in the environment is
also responsible for determining the sexes in aphids. Miss
Stevens, however, has recently shown that what appears to be a
change in sex should rather be regarded as a change from the
parthenogenetic to the sexual mode of reproduction.3 According
to this view the sex of each individual is determined by the
character of the gamete or gametes by which it is developed.
The supposed influence of food and external conditions upon
sex-determination in various kinds of insects, and other animals,
is discussed at some length in a future chapter of this work
(Chapter XV.).
Semper pointed out long ago that the occurrence of repro-
duction (or of the particular mode of reproduction), with
1 Semper, loc. cit. z Morgan, loc. cit.
3 Stevens, " Studies in the Germ-Cells of Aphids," Carnegie Institution
Report, Washington, 1906.
THE BREEDING SEASON 13
insects as with other animals, depends, among other things,
upon the nature of the diet, upon the chemical conditions of
the surrounding medium, upon the moisture of the air, or
upon other circumstances which are often unknown. Thus,
failure to breed in a new environment is experienced by many
Lepidoptera. For example, Death's-Head hawk moths, which
are commonly blown over to this country from the Continent,
but do not breed here, deposit their eggs on young potato plants,
and these develop into moths which emerge in the autumn.
The eggs, however, are quite infertile, so that, as a result, the
Death VHead has never established a footing in Britain, though
stray specimens are often captured.1 In the case of other insects,
such as the mosquito (Anopheles), there is direct evidence that
food is an important factor in egg-formation. Thus it was
found that mosquitoes fed on bananas refused to breed, but
when fed on human blood they invariably laid eggs after two
or three days.2 It is interesting to note also that in the mos-
quitoes and other Culicidse, the males are generally unable
to suck blood, this habit being apparently correlated with the
function of oviposition. Dr. Gordon Hewitt informs me that
among the Empidse, which are carnivorous, the females, during
the nuptial flights, are always fed by the males on small insects,
and that they seem incapable of discharging their sexual func-
tions unless they are fed in this way.3
In some insects oviposition takes place long after the death
of the males. Thus, Lefroy and Hewlett state that in the
mango weevil (Cryptorhynchus gravis) the males die in August
while the females live until the following March to lay eggs.4
MOLLUSCA
Among the marine Mollusca, in curious contrast to so many
forms of life, winter is the usual time for the deposition of the
1 Country Side, October 27, 1906.
2 " Eeport of Malaria Expedition to Nigeria," Liverpool, Trop. Med.
Memoir, IV. See also Ross (Nature, vol. Ixxx., 1909), who says that females
of Culex and Stegomya apparently only desire to suck blood after fertili-
sation.
3 Hewlett, "Coupling of Empis," Ent. Mag., vol. xliii., 1907.
4 Lefroy and Hewlett, Indian Insect Life, Calcutta, 1909.
14 THE PHYSIOLOGY OF REPRODUCTION
eggs.1 On our own coasts Nudibranchs come to shore to lay
their eggs from January to April. Patella spawns from October
until the end of the year. Purpura lapillus is said to be most
active during the same season, but it breeds to some extent
throughout the year. Buccinum undatwn breeds from October
until May, whereas Littorina breeds all the year round.2
Among the land-Mollusca there is a more marked periodicity
in the breeding season than among the marine forms. In
temperate climates breeding is restricted to the summer. In
the tropics the occurrence of the breeding season is generally
determined by the alternations of wet and dry seasons. In
other cases, where there are no great seasonal changes, the
land-Mollusca may breed all the year round.3 The snails of
the Mediterranean area, according to Semper, arrive at sexual
maturity when they are six months old, and before they are
fully grown. Those individuals which reach this age in the
spring deposit eggs a second time after the heat of the summer
is over, and so experience two breeding seasons in the year,
with an interval of a few months between them during the
hot weather. Semper shows, further, that individuals of the
same genera, or perhaps even of the very same species, in the
damper and colder climates of the north, do not lay eggs till
development is complete ; while in the dry, warm region of the
Mediterranean, they have produced two lots of eggs before they
are fully grown. This is because completion of growth and
sexual maturity do not necessarily coincide. In a similar way,
in the pond-snail (Limncea) the minimum of temperature which
admits of the assimilation of food, and so of growth, is much
above the winter temperature of egg-deposition.
In tropical climates, where the variation in temperature
throughout the year is reduced to a minimum, the periodicity
in the breeding habits of animals is to a considerable extent
obliterated, at least in so far as it is dependent upon tempera-
1 Lo Bianco, " Notizie biologische riguardanti specialmentc il periodo di
maturita sessuale degli animali del golfo di Napoli." Mitth. Zool. Stat. NcapoL,
vols. viii. and xiii. Much valuable information concerning the breeding
habits of Mollusca and other animals, inhabiting the Bay of Naples, is given
in these papers.
2 Cook, "Mollusca," Camb. Nat. Hist., vol. iii., London, 1895.
3 Semper, loc. cit.
THE BREEDING SEASON 15
ture. Semper 1 says that few things impressed him more in the
Philippine Islands than the absence of all true periodicity in the
breeding habits not only of the land-molluscs, but also of the
insects and other land-animals. " I could at all times find~
eggs, larvae, and propagating individuals, in winter as well as in
summer. It is true that drought occasions a certain periodicity,
which is chiefly perceptible by the reduced number of in-
dividuals in the dry months, and the greater number in the
wet ones ; it would seem that a much smaller number of eggs
are hatched under great drought than when the air is very
moist. Even in January, the coldest and driest month, I found
land-snails which require much moisture, and at every stage
of their development, but only in shady spots, in woods, or by
the banks of streams. But what was far more striking in these
islands was the total absence of all periodicity in the life of the
sea-animals, particularly the invertebrata ; and among these I
could not detect a single species of which I could not at all
seasons find fully grown specimens, young ones, and freshly
deposited eggs." Semper goes on to remark that even in
some cold seas periodicity is far more often eliminated than is
commonly supposed, and mentions that the eggs of the sea-
mollusc, Tergipes, have been found at all seasons, like those of
Littorina on our own coasts.
ECHINODERMATA
Sea-urchins and starfish, and other Echinodermata, appear
generally to have a regularly recurrent breeding season, at
which the genital organs swell up to an enormous size. In the
sea-urchin, Echinus esculentus, these organs grow into huge
tree-like structures with branched tubes, lined by the sexual
cells. These are sold for food by the fishermen in Naples, who
call them " frutta di mare/' It is said that a single female
E. esculentus will produce as many as 20,000,000 eggs in a
breeding season. At other times of the year the generative
organs are so reduced as to be scarcely recognisable. E. esculentus
at Port Erin, in the Isle of Man, spawns in June.2 At Dunbar, in
1 Semper, loc. cit.
2 Chadwick, Liverpool Marine Biological Committee Memoirs, vol. iii.,
Echinus, Liverpool, 1900.
16 THE PHYSIOLOGY OF REPRODUCTION
Scotland, it has been observed to spawn at the same time. The
sea-urchins at Naples spawn at the end of the year (E. acutus
being mature in November and December, and E.microtuberculatus
from September onwards).1
CEPHALOCHORDATA
In the lancelet (Amphioxus lanceolatus) of the Mediterranean
the breeding season extends from spring until autumn, the
glands becoming so large by the ripening of ova and spermatozoa
that the atrium is used up to its utmost capacity. Spawning,
when it occurs, invariably takes place about sun-down (i.e.
between 5 and 7 P.M.), and never, so far as known, at any
other time.2
PISCES
Among fishes the duration of the breeding season varies
considerably according to the group to which they belong.
The ova of Elasmobranchs are deposited singly or in pairs at
varying intervals throughout a great part of the year. In
Teleosts, on the other hand, the breeding season is limited as a
rule to the spring and summer in temperate ch' mates. In a
single individual spawning may last no longer than a few weeks
or even days.3 The enormous number of eggs produced by
most Teleosts must be connected with the absence of internal
fertilisation, involving a large wastage of ova which never come
in contact with male cells or spermatozoa.
The cod, off our own coasts, has a spawning season ex-
tending from January to June, but the majority of individuals
spawn in March. It has been found, however, that in some
parts of the North Sea the cod may spawn in the autumn. In
the whiting the spawning period lasts from early March until
the third week in August.4 The investigations of the Marine
1 Lo Bianco, loc. cit. The spawning times of most of the Naples
Echinoderms are given in these memoirs.
2 Willey, Amphioxus and the Ancestry of the Vertebrates, New York,
1894.
3 Bridge, "Fishes," Camb. Nat. Hist., vol. vii., London, 1905.
4 Masterman, "A Contribution to the Life-Histories of the Cod and
Whiting," Tram. Roy. Soc. Edin., vol. xl., 1900.
THE BREEDING SEASON 17
Biological Association have shown that in the plaice of the
South Devon bays the maximum spawning period is between the
third week of January and the second week of February. This
period in the North Sea and Irish Sea would appear to be slightly^
later. Herdman l records that, in the year 1904, the plaice in
the open-air ponds at the Port Erin Biological Station started
spawning on March 3, and those at the Peel (Lancashire) Sea
Fish Hatchery (under cover) on March 1.
In the Holostean fish, Lepidosteus, which lives in the fresh
waters of North America, the breeding season recurs with a
wonderful regularity about May. At this time the fish resort in
large numbers to shallower water, where the temperature is
higher. Here the ova and spermatozoa are emitted during
recurrent periods of sexual excitement.2 The related fish, Amia,
of Central and Southern North America, spawns usually in May,
the exact season depending somewhat upon the temperature of
the water. The fish make their way from deep water to the
shallow spawning place, which is generally at the end of a
swampy lake.3
In the Crossopterygian fish, Polypterus bichea, the ova ripen
in the summer months from June to September, the breeding
season depending upon the period of inundation, as in most
of the Nile fishes.4 The other species of Polypterus (P. senegalis
and P. laprodei), which inhabit the river-basins of tropical
Africa, spawn also in the wet season in July and August.5
In the Dipnoan, Ceratodus, of Australia the principal time
for spawning is September and October, at the end of the dry
1 Herdman, " Spawning of the Plaice," Nature, vol. Ixix., 1904. See also
Wallace (W.), same volume. For information concerning the spawning seasons
of different species of fish, The Journal of the Marine Biological Association, the
publications of the English and Scottish Fishery Boards, and the International
Council for Fishery Investigation, should be consulted. These reports show
that the migratory and reproductive periods of fishes are affected by the
temperature, salinity, &c., of the sea.
2 Agassiz, "The Development of Lepidosteus," Proc. Amer. Acad. Arts
and Science, vol. xiv., 1878.
3 Bashford Dean, " The Early Development of Amia," Quar. Jour. Micr.
Science, vol. xxxviii., 1895.
4 Harrington, "The Life-Habits of Polypterus," American Naturalist,
vol. xxxiii., 1899.
5 Budgett, " On the Breeding Habits of Some West African Fishes,"
Trans. Zool. Soc., vol. xvi., 1901.
B
18 THE PHYSIOLOGY OF REPRODUCTION
season.1 In the other two Dipnoans, Lepidosiren of South America
and Protopterus of Africa, spawning occurs shortly after the
emergence of the fish from their summer sleep. Kerr, writing
of the former, says that the exact time for breeding varies
greatly from year to year in correlation with the extreme varia-
bility of the climate, the swamps, which the mud-fish inhabit,
sometimes remaining dry for prolonged periods.2
Many fishes migrate, before the commencement of the
breeding season, to localities suitable for the deposition of their
eggs. Thus, certain marine fishes like the salmon, the shad,
and the sturgeon ascend rivers for long distances before spawn-
ing ; others merely migrate to shallower water nearer shore.
The eel, on the other hand, is a fresh-water fish which migrates
to the sea for breeding, and deposits its eggs in deep water.
Jacobi 3 showed that the migration of the eel is not deter-
mined by the growth of the genital organs, for these do not begin
to develop until the fish have reached the sea. He concluded,
therefore, that eels need salt water before the genital organs
can develop. Similarly, Noel Pa ton 4 has pointed out that
salmon, with their genitalia in all stages of development, are
ascending the rivers throughout the whole year.
Miescher,5 too, has shown that salmon go practically without
food so long as they are in fresh water, being nourished by the
large store of material which they accumulated while they
were in the sea. This observation has been confirmed by Noel
Pa ton. Miescher and Pa ton have shown, further, that the gain
in solid material (proteins, &c.), by the genitalia,6 as the fish pass
up the rivers, is met by a loss in solid material in the muscles.
This transference is not brought about by anything of the nature
of a degeneration taking place in the muscles ; but the latter
appear simply to excrete or give out the material which has been
1 Seraon, In the Australian Bush, London, 1899.
2 Kerr, " The External Features in the Development of Lepidosiren
paradoxa," Phil. Trans. B., vol. cxcii., 1900.
3 Jacobi, Die Aalfrage, Berlin, 1880.
4 Paton, Fishery Board Report of Investigations on the Life History of the
Salmon, Glasgow, 1898.
6 Miescher, Histochemische und Physiologische Arbeiten, vol. ii., Leipzig,
1897.
6 The gain in the genitalia is due largely to the formation of compara-
tively simple proteins (protamines, histones, &c. ). See Chapter VIII.
THE BREEDING SEASON 19
accumulated in them. It should be noted, however, " that the
gain of solids by the genitalia is small as compared with the loss
of solids by the muscle, that in fact the greater part of the
solids lost from the muscles are used up for some other purpose
than the building up of the genitalia/' l Pa ton concludes that
the state of nutrition is the main factor determining migration
towards the river, and that, when the salmon has accumulated
a sufficiently large store of material, it returns to the rivers
which were its original habitat. It does not seem possible,
however, to maintain that nutrition is a determining influence
in the growth of the genital glands, since these are undeveloped
when the fish begin to migrate and enter upon their period of
starvation.
Wiltshire 2 states that in some fishes, at the period of ovi-
position, the lips of the genital orifice swell and become congested.
This condition he regards as comparable to that which occurs
during the " heat " period of a mammal.
AMPHIBIA
The intimate connection between sexual periodicity and
climatic variation exhibited by many Amphibia and Reptilia,
especially in temperate climates, was commented on by Spallan-
zani.3 This close dependence upon environmental conditions is
evidently due largely to the habits of life of these animals, many
of which hibernate or show great sluggishness in cold weather ;
while among Amphibia it must be associated with the further
fact that, whereas most members of the group live to a great
extent upon. land, it is necessary for them to deposit their eggs
in water. Spallanzani concludes that the reason why Amphibia
are subject to a variation which is not observable in birds and
Mammals is because the former, like insects, are cold-blooded,
and have a comparatively small supply of internal heat to
1 Paton, loc. cit. Milroy ( ' ' Chemical Changes in the Muscles of the Herring
during Reproductive Activity," Seventh International Congress of Physiolo-
gists, Heidelberg, 1907; abstract in Zeit. f. Phys., vol. xxi.f 1907; and
Biochem. Jour., vol. iii., 1908) has recently shown that similar changes take
place in the herring, in which, however, the starvation period is briefer.
2 Wiltshire, " The Comparative Physiology of Menstruation," Brit. Med.
Jour., 1883.
3 Spallanzani, Dissertations, vol. ii., London, 1784.
20 THE PHYSIOLOGY OF REPRODUCTION
animate them when it is cold. " As therefore the exercise of
their functions depends on the heat of the atmosphere, their
amours will also depend upon this cause, and will, of course, be
later in cold than in hot climates, and in both will vary with
the season/'
Spallanzani illustrates the truth of this fact by pointing out
that various species of frogs and toads begin to propagate
earlier in Italy than in Germany or Switzerland.1 On the other
hand he records the observation that the tree-frog and the fetid
terrestrial toad were copulating in the ponds and reservoirs of
Geneva in March, at a time when in Lombardy they had not
yet quitted their subterranean abodes.
It is interesting to note that in the frog and other Amphibia
the ova are produced in winter, when the animals eat little or
nothing, just as the genital organs of the salmon develop during
the period of migration, when the fish have practically ceased
to feed.
Bles 2 has discussed at some length the conditions under
which it is possible to induce various species of Amphibia to
breed in captivity. He states that the most necessary con-
dition is that the animals should be allowed to hibernate at
the proper season, and in order to accomplish this they must
be in thoroughly good health when the winter sets in, having
passed the summer in the best circumstances in regard to light,
heat, and supply of food. Bles's observations relate more
especially to the African frog, Xenopus Icevis, but he believes
his conclusions to apply in a large degree to many other species
of Amphibia.
The frogs in question were kept in a " tropical aquarium "
(that is to say, an aquarium which could be kept at a tropical
temperature by regulating a heating apparatus). In the summer
the temperature was maintained at about 25° C. ; in December
1 In the common frog (Rana temporaria) the usual time for spawning in
Middle Europe is March, earlier in warm, later in cold seasons; in southern
countries, January or February, but in Norway not until May. Vide Gadow,
Cambridge Natural History, vol. viii., London, 1901. This book contains a
quantity of valuable information concerning the breeding habits of many
Amphibia and reptiles.
2 Bles, "The Life-History of Xenopus lavis," Trans. Hoy. Soc. Edin.,
vol. xli., 1905.
THE BREEDING SEASON 21
it was allowed to drop to 15°— 16° C. during the day, and
5°-8° C. during the night. The bottom of the aquarium was
covered with earth and stones, on which the weed Vallisneria
thrived. The water in the aquarium was never changed. The
frogs were fed daily upon small worms, or strips of liver, until
they would eat no more. During winter they became lethargic,
taking very little food. When the temperature rose in the
spring and the days became brighter, the frogs became more
active, especially the males. At this time breeding could be
induced by a certain method of procedure which Bles describes
as follows : " First, the temperature of the aquarium is raised
to 22° C. ; and secondly, when it has become constant, a certain
amount of water, say two gallons, is drawn off morning and
evening, allowed to cool for twelve hours, and then run in
slowly in the following manner, in order to simulate the fall of
rain. The cooling vessel is raised above the level of the
aquarium, and a syphon is used to run off the water. The lower
end of the syphon is drawn out to a fine point, and turned up
in such a way that the water rises up like from a fountain, and
falls as spray into the aquarium. ... By carrying out such
measures I obtained from one female, between April and July
1903, more than fifteen thousand eggs/'
The abdomen of the female Xenopus is stated to become very
much distended during the winter by the enormously enlarged
ovaries. " The three flaps surrounding the cloacal aperture are
flaccid until the spring, when they become swollen and turgid,
and more highly vascularised." (Cf. the changes in the female
genital organs of Mammals during the " heat " periods, de-
scribed in the next chapters.) The male Xenopm is said to
assume its nuptial characters two days after the temperature
is raised to 22° C., and a very little later it becomes vocal, the
voice strengthening from day^to day. Copulation takes place
only at night, and spawning may commence an hour afterwards ;
but this does not occur unless the water is changed in the manner
above described.
According to Leslie l it would appear that Xenopus, in its
native country, breeds only in August, i.e. in the South African
1 Leslie, "Notes on the Habits and Oviposition of Xenopus Icevis," Proc.
Zool. Soc., 1890.
22 THE PHYSIOLOGY OF REPRODUCTION
spring. Bles, however, is disposed to think that Xenopus, like
Discoglossus in the wild state, may breed several times during
the spring and summer, since the frogs in confinement in some
years spawned three times.
Semper 1 has shown that if axolotls are kept crowded together
in small aquaria, without plants or seed, individuals which are
sexually mature will not deposit ova even though the water be
changed and abundant food supplied. But if they be suddenly
transferred to aquaria stocked with plants, and with stones and
sand on the bottom and running water, they can be induced
to spawn within a few days, and may do so as often as three or
four times a year. Bles states that he is able to confirm Semper 's
observations upon axolotls, and that he obtained similar results
by treating individuals of Triton waltlii and of Discoglossus in
the same way.
Annandale 2 states that in the Malay Peninsula Rhacophorus
leucomystax and Rana limnocharis appear to breed only after a
heavy fall of rain, and he concludes that the stimulus set up
by falling water is necessary before the sexual impulse can be
induced.
Thus there appears to be abundant evidence that breeding
in mature Amphibians does not occur cyclically merely, but it
takes place only in response to certain definite external stimuli.
Bles remarks that if this view is correct, and assuming it to
apply to other groups besides the Amphibia, it helps to explain
why many animals fail to breed in captivity ; and also how it is
that others (e.g. insects), in a state of nature, appear in large
numbers in one year and are much less numerous in another.3
It is interesting to note that among frogs and other cold-
blooded Vertebrates there is a periodicity in the occurrence of
their reflex responses.4 It has been shown that if the region
1 Semper, " Ueber eine Methode Axolotl-Eier jederzeit zu erzeugen," Zool.
Anz., vol. i., 1878. See also Animal Life.
2 Annandale, Fasciculi Malaycnscs, ZooL, Part I. 1904.
3 See page 5, Chapter I.
4 The sexual posture of frogs in the act of copulation is maintained as a
spinal reflex. The tortoise is similar. The reflex is inhibited by excitation
of the optical lobes. (Spallanzani, loc. cit. ; Goltz, Zeut. f. deutsch. mcd. Wiss.,
1865-66 ; Tarchanoff, Pfluger's Arch., vol. xl., 1887 ; Albertoni, Arch. Ital. de
£iol., vol. ix., 1887).
THE BREEDING SEASON 23
of the shoulder-girdle bearing the four limbs, together with the
connected skin and muscles, and the three upper segments of
the spinal cord, are cut out from the male frog during the breed-
ing season (but not at other times), the irritation of the skin
will cause a reflex, clasping movement, similar to that char-
acteristic of the normal male at this period. In spring and
early summer, after reviving from their winter sleep, frogs tend
to be irregular in certain other of their reflex responses. MacLean
has shown that in the heart of the frog, newt, and salamander,
and also the eel, vagus inhibition is absent or markedly diminished
at certain periods corresponding roughly to the seasons of sexual
activity,1 but the significance of the changes is not very apparent.
REPTILIA
Reptiles which hibernate usually begin to breed shortly
after the commencement of the warm weather which terminates
the hibernating period, just as in the case of Amphibia. Other
reptiles, which live in warm or tropical climates, also have
regularly recurrent breeding seasons, in some cases extending
over many months, generally in the spring and summer.2 It
would seem that in reptiles also, breeding only occurs in
response to certain external stimuli, and that temperature is
the main factor, as supposed by Spallanzani.
AVES
It would appear almost superfluous to cite examples of
sexual periodicity from among birds. That spring and summer
are the seasons when most birds pair, build their nests, and
incubate their eggs, and that these processes are wont to vary
slightly with the character of the season, are facts that are
familiar to all. Bird-fanciers know also that the capacity of
certain birds for egg-laying may be influenced by diet, and that
this capacity can sometimes be increased (e.g. in the common
fowl 3) by the supply of suitable food.
1 MacLean, "The Action of Muscarin and Pilocarpin on the Heart of
certain Vertebrates, with Observations on Sexual Changes," Biochem. Journal,
vol. iii., 1908.
2 See Gadow, loc. cit.
3 Wright, The New Book of Poultry, London, 1902.
24 THE PHYSIOLOGY OF REPRODUCTION
With the approach of the breeding season the genital organs
grow enormously until the whole oviduct reaches a state of
hypertrophic turgescence. Gadow states that in the common
fowl the oviduct at the period of rest is only six or seven inches
long and scarcely a line wide, but that at the time of egg-laying
it becomes more than two feet in length and nearly half an inch
in width, thus increasing the volume about fifty times. This
remarkable growth occurs annually. Gadow remarks also that
the testes of the house-sparrow increase from the size of a
mustard-seed to that of a small cherry, and in so doing tem-
porarily displace the usual arrangement of the viscera in the
body-cavity.1
A very large number of birds seasonally migrate, and this
habit, as in the case of the migratory fish already referred to, is
closely associated with the function of breeding.2 Jenner 3
stated long ago that migration was invariably associated with
an increase in size of the ovaries and testes, and that when
these begin to shrink, after discharging their functions, the birds
take their departure. Thus the ovaries of the cuckoo are stated
to be almost atrophied in July. It would seem quite possible
that the annual development of the sexual organs is the
immediate stimulus which, in the individual, fixes the time for
the spring migration, for it is known that in birds passing
northward the ovaries and testes are well developed. (But cf.
fishes, p. 18.) Thus wading birds, such as the sanderling shot
by Mr. Eagle Clarke at Spurn Head, in May, were found by him
to have their sexual organs in a very advanced state of growth.
These birds were probably on their way to Greenland or Siberia.
Schafer 4 has suggested that the migratory impulse is deter-
1 Gadow, Article on "Reproductive Organs," in Newton's Dictionary of
Birds, London, 1893-96. Disselhorst also (" Gewichts- und Volumszunahmen
der mannlichen Keimdriisen," Anat.Anz., vol. xxxii., 1908) has called attention
to the enormous increase in size and weight of the testicles and ovaries in
many birds (and also in some Mammals) in the breeding season. Thus, in
Fringilla, the testicles may increase three-hundred-fold.
2 For much of the information given here regarding migration, I am in-
debted to Mr. Eagle Clarke.
3 Jenner, " Some Observations on the Migration of Birds," Phil. Trans.,
Part I., 1824.
4 Schafer, "On the Incidence of Daylight as a Determining Factor in
Bird Migration," Nature, November 7, 1907.
THE BREEDING SEASON 25
mined by the relation of daylight to darkness, having been
brought into being through the agency of natural selection, in
consequence of the necessity to most birds of daylight for the
procuring of food. This hypothesis explains both the northerly^
migration in spring and the southerly migration in autumn,
since at both times the birds are travelling in the direction of
increased light (or, if they start before the equinox, towards
regions where they will enjoy longer daylight later in the season).
The suggestion that the time of the spring migration is deter-
mined in each individual by a stimulus set up by the growing
genital organs is in no way opposed to Schafer's theory, which
provides an explanation of the general fact of migration.
It has been noted that the northerly spring migration is far
more hurried than the somewhat leisurely autumn migration in
the reverse direction. Furthermore, although the north-south
migratory movements are as a rule extraordinarily regular, it
has been observed that the birds do not all set out together,
and that the times of departure and arrival for each species
may vary in any one year by several weeks. Moreover, golden
plover are found migrating across Britain on their way north-
ward (perhaps to Iceland) at a time when other individuals of
the same species are rearing young in Britain. (The breeding
season in Iceland is about a month or six weeks later than in
Britain.) In view of these facts it is evident that the occurrence
of the migratory movement is dependent not merely upon
external or environmental influences, but also upon internal
or individual ones, and, as already stated, it is not improbable
that one of the factors involved is the state of development of
the organs of generation.
Many birds are double-brooded, having young ones not only
in spring, but also in autumn before the close of the mild weather
(in temperate climates). Swifts are stated to have a second
brood in Southern Europe after leaving Britain in August, and
the same is said to be the case with nightingales. Wiltshire l
mentions that a pair of swifts that stayed behind the others,
had a brood in September, which migrated with the parent
birds in October. Whether birds are single- or double-brooded
probably depends to a large extent upon the duration of the
1 Wiltshire, loc. cit.
26 THE PHYSIOLOGY OF REPRODUCTION
period of incubation. This period in wading birds and sea-birds
is approximately double that of passerine birds ; but, within the
limits of the group to which they belong, it is closely related to
the size of the birds. Thus the incubation-period of the stormy
petrel is thirty days ; that of the starling is fifteen or sixteen
days ; while that of the raven (the largest passerine bird) is
about nineteen days. The starling is, as a rule, almost certainly
double-brooded, while the petrel and the raven are single-
brooded.1 Other birds, such as the sparrow, are probably often
treble-brooded. It is, of course, well known that domestication
tends to increase the number of broods which a bird may
produce (e.g. in pigeons and poultry).
MAMMALIA
The breeding season in the Mammalia, and the variations
in its periodicity, are discussed at some length in the next
chapter. Here it will suffice to point out that whereas the
occurrence of breeding in any one country or locality is closely
connected with the climatic conditions and the periodicity of
the seasons in that country, this rule does not hold invariably.
For while the sheep in South Africa breeds in April and May
(the South African autumn), thus following the seasons (since
sheep breed ordinarily in autumn in this country), the camels
in the Zoological Gardens in London experience rut in early
spring, or at approximately the same time as the breeding
season of the wild camels in Mongolia.2 It has been already
noted that some Mammals refuse to breed in captivity, while
in many others the occurrence of breeding can be regulated to
some extent by such factors as accommodation, heating, arid
feeding. Also in certain domestic animals, such as the sheep,
the condition of " heat " can be induced more readily by the
supply of additional or special kinds of food.3
1 I am indebted to Mr. Eagle Clarke for certain of this information.
2 Heape, "The Sexual Season of Mammals," Quar. Jour. Micr. Science,
vol. xliv., 1900. The black swans in the Zoological Gardens breed at the
same time as those in Australia. (Cf. also Timor pony, p. 51.)
3 Cf. birds, p. 23, and insects, p. 13. This point is referred to more
fully in Chapter XIV., where the causes which influence fertility are dis-
cussed.
THE BREEDING SEASON 27
The approach of the breeding season in many animals, if
not in most, is marked by a display of greater vitality, as mani-
fested by an increased activity, which relates not merely to the
sexual organs but to the whole metabolism of the body. This"
enhanced vitality is, as a rule, maintained throughout the
breeding season. Thus male birds at the time of pairing are
in a state of the most perfect development, and possess an
enormous store of superabundant energy. Under the influence
of sexual excitement they perform strange antics or rapid flights
which, as Wallace remarks, probably result as much from an
internal impulse to exertion as from any desire to please their
mates. Such, for example, are the rapid descent of the snipe,
the soaring and singing of the lark, the strange love-antics of
the albatross, and the dances of the cock-of-the-rock, and of
many other birds.1 The migratory impulse, which, as already
mentioned, is closely associated with the periodic growth of the
sexual organs, may also very possibly be regarded as affording
evidence of increased vitality at the approach of the breeding
season. Moreover, many of the secondary sexual characters,
both those of the embellishing kind and others as well, are
developed during only a part of the year, which is almost
invariably the period of breeding.
A familiar example of this correspondence between the
development of secondary sexual characters and the activity
of the reproductive organs is supplied by the growth of the
antlers in stags. At the time of rut, which in the red-deer
(Cervus elaphus] begins in September or October (see p. 48),
the antlers, or branched outgrowths from the frontal bones, are
completely developed, having shed their " velvet " or covering
of vascular skin. The animals during this season are in a state
of constant sexual excitement, and fight one another with their
antlers for the possession of the hinds.2 By the end of the year
the fighting and excitement have ceased, and the stags begin
once more to herd together peaceably, and apart from the females.
Shortly afterwards the antlers are shed. In most parts of
Britain this occurs about April ; but a Highland stag has been
1 Wallace (A. R.), Danvinism, London, 1890.
2 The larynx also is said to enlarge at this season, when the stag is wont
to utter a loud bellowing noise.
28 THE PHYSIOLOGY OF REPRODUCTION
known to drop his antlers as soon after the rutting season as
December, while, on the other hand, some immature animals
in the Lake District are said to carry them until May. After
the shedding of the antlers new ones begin to grow from the
pedicles, the growth taking place chiefly in July and August.
When the new antlers have reached their full development
the " velvet " is shed (about the beginning of September). The
size of the antlers, and the number of branches or " points/' go
on increasing every year throughout the reproductive period of
the stag's life and until he begins to decline with old age.1
In the American prongbuck (Antilocapra americana), which
is unique among hollow-horned ruminants in shedding the horns
every year, the shedding follows the rutting season more closely
than in the stag. The rutting in this species begins in September,
and lasts about six weeks. In old bucks the horns are shed in
October, while the new growth is not completed until July or
August in the following year.2
A secondary sexual character of a comparable kind occurs in
the male salmon, in which the tip of the lower jaw, during the
breeding season, is turned up and enlarged, as if to protect the
fish in fighting when charged by another male.3
In Polypterus , during the breeding season, the oval fin of the
male becomes greatly enlarged and thickened, and has its
surface thrown into folds between the fin-rays. The object of
this modification is not known.4
The papillae on the hind limbs of the breeding male
Lepidosiren are structures which seem to possess a special
significance, since Kerr 5 has shown that they probably serve as
accessory organs of respiration. During the greater part of
the year they are relatively inconspicuous ; but as soon as the
animal is set free at the beginning of the wet season, they begin
to grow with remarkable rapidity, forming slender filaments
two or three inches in length and blood-red in colour from their
intense vascularity. After the breeding season is over the
filaments commence to atrophy, and eventually shrink to their
1 Cunningham (J. T.), Sexual Dimorphism, London, 1900.
2 Cunningham (J. T.), loc. cit.
3 Darwin, Descent of Man, Popular Edition, London, 1901.
4 Budgett, loc. cit. 5 Kerr, loc. cit.
THE BREEDING SEASON 29
former size, but still present for some time a distinctive ap-
pearance owing to their being crowded with black pigment-cells.
Whatever may be the precise purpose of this curious modifi-
cation it is certain that its development is associated with
reproductive activity, and so may be regarded as an expression
of the intense vitality which the organism exhibits at this period.
Some animals exhibit in the breeding season a particularly
vivid coloration which is absent from them at other times. The
case of the male dragonet (Callionymus lyra), which becomes a
brilliant blue-and-yellow colour, has been discussed at some
length by Cunningham,1 who concludes that the production of
the guanin and pigment that give rise to the colour is to be
connected with the intense nervous excitement which affects the
fish at the time of courtship. " Physiological processes are
known to be governed largely by nervous impulses, and not
merely the circulation, but the excretory activity of the skin,
are known to be influenced by nervous action. Pigment and
guanin are produced in the skin by the secretory or excretory
activity of the living cells." 2 Whatever be the precise ex-
planation of this particular instance of intenser coloration,
there can be no doubt that it is an indication of a more active
metabolism.
The brilliant colours of the male lump-sucker (Cydopterus
lumpus), and of other fish 3 at the time of breeding, are probably
due to the same causes as in the dragonet.4
1 Cunningham (J. T.), loc. cit. 2 Cunningham (J. T.), loc. cit.
3 Numerous instances are given by Darwin, loc. cit., both for fishes and
Amphibians.
4 The nuptial changes which occur in fishes are not necessarily in the
direction of increased brilliance of coloration. Miss Newbigin describes
these changes in the salmon as follows: "When the fish comes from the
sea the skin is of a bright silvery hue, while the flesh has the familiar
strong pink colour. The small ovaries are of a yellow-brown colour. As
the reproductive organs develop during the passage up the river, certain
definite colour-changes occur. The skin loses its bright silvery colour, and,
more especially in the male, becomes a ruddy-brown hue. At the same time
the flesh becomes paler and paler, and in the female the rapidly growing
ovaries acquire a fine orange-red colour. The testes in the male remain a
creamy white. After spawning the skin tends, in both sexes, to lose its ruddy
colour and to regain the bright silvery tint ; the flesh, however, remains pale
until the kelt has revisited the sea" (Report of Scottish Fishery Board, 1898).
Barrett-Hamilton (Proc. Camb. Phil. Soc., vol. x., 1900, and Annals and
30 THE PHYSIOLOGY OF REPRODUCTION
The tail of the lyre-bird, which is shed at the end of the
breeding season, not to be renewed again in the same form
until the following summer, the brilliant plumage of the breeding
drake, the more intense colouring of the phalarope, and many
other birds during the season of courtship, are familiar instances
of the same kind of phenomena.1 The remarkable plate of horn
which is developed in the upper mandible of the pelican in the
breeding season, and bodily shed at the end of it, and the " gular
pouch " in the throat of the breeding bustard, are examples of
a more special kind, the existence of which, however, must
be connected, either directly or indirectly, with the contem-
poraneous increase of sexual activity and the enhanced vitality
which accompanies it.
In some animals certain glandular organs, apart from those
concerned in the reproductive processes, show a special activity at
the breeding season. For example, in the swiftlets (CollocaMa)
the salivary glands become peculiarly active, and secrete a sub-
stance which is allied to mucin, and is employed in building
the edible birds'-nests of Chinese epicures.2
A somewhat similar peculiarity exists in the male of the
sea-stickleback (Gusterosteus spinachia), which binds together the
weeds forming its nest by means of a whitish thread, secreted
by the kidneys, and produced only during the breeding season.
According to Mobius, as quoted by Geddes and Thomson,3 the
Mag. of Nat. Hist., vol. ix., 1902) draws attention to many such sexual
phenomena, and more especially to those occurring in the spawning season
in certain salmonoid fishes of the genus Onchorhynchus. The fish undergo
extraordinary changes in colour and shape, and, since they die when spawning
is accomplished, it is argued that the changes cannot have any aesthetic
significance, but represent a pathological condition in which the fish become
continually more feeble and eventually succumb.
1 Beebe (" Preliminary Report on an Investigation of the Seasonal
Changes of Colour in Birds," Amer. Nat., vol. xlii., 1908) describes an experi-
ment in which certain tanagers and bobolinks, which had been prevented
from breeding, were kept throughout the winter in a darkened chamber
with a somewhat increased food-supply. As a consequence the nuptial
plumage was retained until the spring, when the birds were returned to
normal conditions. They shortly afterwards moulted. The breeding plumage
was then renewed, so that in this case the dull winter plumage was never
acquired.
2 Geddes and Thomson, Evolution of Sex, Revised Edition, London, 1901.
3 Geddes and Thomson, loc. cit.
THE BREEDING SEASON 31
secretion is semi-pathological in nature, being caused by the
mechanical pressure of the enlarged testes upon the kidneys.
The male gets rid of the thread-like secretion by rubbing itself
against objects, and thus, by an almost mechanical process, the
weaving habit is supposed to have become evolved.
During the breeding season the anal scent-glands of snakes
are said to be actively functional, but not at other times. A
similar fact is stated about the submaxillary glands of crocodiles,
and the cloacal glands of tortoises and other reptiles.1 The
secretions of these glands, like the musk glands of Mammals,
no doubt serve the purpose of enabling the sexes to detect one
another's presence more easily. (See p. 241.)
The periodicity which is such a marked feature of animal
life in temperate climates has been discussed at some length
by Semper.2 This author concludes that the phenomenon in
question is dependent on the severe extremes of summer and
winter temperature to which the animals are exposed. " Every
individual requires a certain duration of life to achieve its in-
dividual development from the egg to sexual maturity and full
growth ; the length of time requisite for this is very various,
and, above all, bears no proportion to the size attained. . . .
This length of time, which we may generally designate as the
period of individual growth, is not alike even for all the in-
dividuals of the same species ; on the contrary, it depends on
the co-operation of so many different factors that it must
necessarily vary considerably. Now, if from any cause the
period of individual growth, say of the salmon, became changed
in consequence of the slower development of the embryo in the
egg or of the young larvae, most or all the young salmon thus
affected would die in our climate, because the greater heat of
spring is injurious to them at that stage/' In a similar way
it may be argued that the periodicity of the breeding season,
no less than the rate of growth, is governed by the necessities of
the youftg. No doubt this is true to a large extent, yet at the
same time it is equally evident, as has been shown above in
numerous instances, that this periodicity is greatly affected by
1 Owen, Anatomy of Vertebrates, vol. i., London, 1866. Laycock, Nervous
Diseases of Women, London, 1840.
2 Semper, Animal Life, London. 1881
32 THE PHYSIOLOGY OF REPRODUCTION
climatic and environmental changes, and even by stimuli of a
more particular nature (cf. frogs, p. 20). But this power, which
all animals in some degree possess, of responding to altered con-
ditions, may none the less have arisen primarily to meet the re-
quirements of the next generation ; or, to speak more accurately,
that those animals which breed at a certain particular season
(or in response to certain conditions which prevail at that
season) have the advantage in being able to produce a new
generation to which this capacity to respond similarly will be
transmitted. In other words, the restriction of the breeding
habit to certain seasons may have been brought about under
the influence of natural selection to meet the necessities of the
offspring.
Heape, however, has raised the objection l that this view is
inapplicable to the Mammalia, in which there is a period of
gestation of greatly varying length in the different species. If
the theory were correct, why, he asks, do some bats experience
a breeding season in the autumn, and not produce young until
the following June, although only two months are required for
the development of the embryo in these animals ; why do roe-
deer in Germany breed in autumn, while the embryo does not
develop beyond the segmentation stage until the following
spring ; and why does the seal take eleven or twelve months
for gestation when a large dog requires only nine weeks ? Heape
believes that the recurrence of the breeding season is governed
directly by climatic, individual, and maternal influences,2 and
that " variation in the rate of development of the embryo, in
the length of gestation, and in the powers of nursing, are quite
sufficient to provide for the launching of the young at a favour-
able time of the year/'
I cannot altogether concur in Heape 's view of this question.
For it seems to me by no means improbable that whereas the
necessities of the offspring, under changed environmental con-
ditions, may sometimes have been provided for by modifications
1 Heape, '* The Sexual Season of Mammals," Quar. Jour. Micr. Science,
vol. xliv., 1900.
2 Under the heading of "individual influences" Heape includes special
nervous, vascular, and secretory peculiarities of the individual and its habits
of life. The length of the gestation and lactation periods he calls "maternal
influences."
THE BREEDING SEASON 33
in the rate of development or length of gestation, yet in other
cases a similar result may have been effected by alterations in
the season of breeding. The mere fact that breeding in any
one species occurs, as a rule, periodically at a time which is on
the whole well suited to the requirements of perpetuating the
race, is itself presumptive evidence that the periodicity of the
breeding season is controlled (through natural selection) by the
needs of the next generation. Further, the breeding season
having been fixed at one period in the history of the species,
the same season would probably be retained (in the absence of
disturbing factors) by the descendants of that species under the
directive influence of heredity. This view is in no way opposed
to the doctrine that the sexual capacity is developed in the
individual in response to definite stimuli, which are largely
environmental and often seasonal.
The occurrence of a succession of " heat " periods within the
limits of a single breeding season no doubt arose in consequence
of the increased opportunity afforded thereby for successful
copulation. The number and frequency of the " heat " periods
under these circumstances are affected by the conditions under
which an animal lives in just the same kind of way as the
periodicity of the breeding season is affected, as will be shown
in the succeeding chapter on the oestrous cycle in the Mammalia.
Concerning the immediate cause of " heat/' and the nature of
the mechanism by which it is brought about, something will
be said later (Chapter IX.).
The origin of the breeding season is a wider question. For
its complete solution, as pointed out by Heape, a comparative
study of the sexual phenomena in the lower animals is essential,
while, as already remarked, sufficient data for a comprehensive
treatment of this subject do not at present exist.
That the breeding season occurs in some animals " as the
result of a stimulus which may be effected through the ali-
mentary canal is demonstrated by the effect upon ewes of certain
stimulating foods."
" That it is associated with a stimulus which is manifested
by exceptional vigour and exceptional bodily ' condition ' is
demonstrated by the pugnacity of the males at such times, by
the restless activity of the females, by the brilliant colouring of
c
34 THE PHYSIOLOGY OF REPRODUCTION
such widely divergent animals as, for instance, annelids,
amphibia, birds, and mammals, by the condition of the plumage
of birds, and of the pelage or skin of mammals."
'That it is [frequently] associated with nutrition, and that
it is a stimulus gradually collected is indicated by the increased
frequency of the [breeding] season among domesticated mammals
as compared with nearly allied species in the wild state.
:c That it is manifested by hypertrophy and by congestion of
the mucous tissue of the generative organs, and of various other
organs, such as the wattles and combs of birds, the crest of the
newt, and by the activity of special glands, the affection of all
of which may be exceedingly severe, is true.
' These, and many other similar facts, are well known, but
they do not assist in the elucidation of the origin of the function.
' The most they do is to show that the sexual instinct is
seasonal, and that nutrition, whether affected by external or
internal factors, plays an important part in its manifestation." 1
The last proposition may be expressed even more generally
in the statement, already formulated, that generative activity in
animals occurs only as a result of definite stimuli, which are partly
external and partly internal ; while the precise nature of the
necessary stimuli varies considerably in the different kinds of
animals, according to the species, and still more according to
the group to which the species belong.
1 Heape, loc. cit. It should be remembei'ed, however, that many animals,
such as the salmon, have their breeding season after prolonged fasts. See
above. (Cf. also the fur-seal, p. 60.)
CHAPTEK II
THE (ESTROUS CYCLE IN THE MAMMALIA
" Omne adeo genus in terris hominumque ferarumque
Et genus aequoreum, pecudes, picteeque volucres
In furias ignemque ruunt: amor omnibus idem."
— ViRGlL, Georg. iii.
IK describing the sexual processes of the Mammalia, and the
variations in the periodicity of breeding which occur in the
different groups, I have employed the terminology originally
proposed by Heape,1 and afterwards adopted by me,2 in giving
an account of these phenomena in the sheep and other animals.
The terms used may now be defined.
The term sexual season is used by Heape to designate the
particular time or times of the year at which the sexual organs
exhibit a special activity. It is, in fact, employed in practically
the same sense as that in which the expression " breeding
season " is used in the previous chapter. Heape suggests that
it is better to adopt the latter term to denote " the whole of
that consecutive period during which any male or female
mammal is concerned in the production of the young/' since
the expression is often used to include the period of pregnancy
or even the period of lactation. The sexual season is the season
during which copulation takes place, but this only occurs
at certain still more restricted times, the periods of " oestrus "
(defined below). The male sexual season, when there is one, is
called the rutting season ; but in many species the male animals
1 Heape, "The Sexual Season," Quar. Jour. Micr. Science, vol. xliv., 1900.
2 Marshall, " The (Estrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans. £., vol. cxcvi., 1903. " The (Estrous Cycle in the
Common Ferret," Qiiar. Jour. Micr. Science, vol. xlviii., 1904. See also
Marshall and Jolly, " Contributions to the Physiology of Mammalian Repro-
duction : Part I. The (Estrous Cycle in the Dog," Phil. Trans. B., vol. cxcviii.,
1905.
35
36 THE PHYSIOLOGY OF REPRODUCTION
are capable of copulating at any time, whereas in the females
this function is restricted to definite periods.
The non-breeding season or period of rest in a female Mammal,
when the generative organs are quiescent (at least relatively)
and the uterus is normal and comparatively anaemic, and the
animal shows no disposition to seek out a mate, is called by
Heape the Anceitrous period or simply the Ancertrum. This period
is generally considerably prolonged, and in many Mammals
occupies the greater part of the year. Its close marks the
beginning of the sexual season.
The first part of the sexual season is occupied by the Pro-
cestrum. This period is characterised by marked changes in
the generative organs, the uterus becoming congested, while
in the later stages there is often a flow of blood from the external
opening of the vagina. The procestrum is the period often re-
ferred to by breeders as the time when an animal is " coming
on heat/' or " coming in season/'
The next period, GEstrus, or CEstrum (as it is sometimes called),
' ' marks the climax of the process ; it is the special period of
desire in the female ; it is during oestrus, and only at that time,
that the female is willing to receive the male, and fruitful coition
rendered possible in most, if not in all, Mammals." l
The periods of procestrum and oestrus are commonly referred
to together as the " heat " or " brunst " period, and sometimes
as the period of " rut/' 2 and no attempt is then made to dis-
tinguish the time occupied by " coming in season/' and the
time at which the female is ready to receive the male. This
failure to distinguish the two periods (procestrum and oestrus) has
led to much confusion, especially in regard to the nature of the
relation between " heat " in the lower Mammals and menstrua-
tion in the human female. As was first pointed out by Heape,
it is the procestrum alone, and not the entire " heat " period
which is the physiological homologue of menstruation. This is a
point which will be dealt with more fully in the next chapter
of this book.
If conception takes place as a result of coition during oestrus,
1 Heape, loc. cit.
2 The term "rut" is used by Heape in the case of the male only, the
" rutting season," as stated above, being the male sexual season.
THE CESTROUS CYCLE IN THE MAMMALIA 37
this period is followed by gestation ; 3 gestation in its turn, after
a short puerperium or period of recovery, is followed by nursing
or lactation, and the latter is succeeded by another anoestrum
at the close of the breeding season.2
If, on the other hand, conception does not occur during
oestrus, the latter is succeeded by a short Melcestrum, during
which the activity of the generative system subsides and the
organs gradually resume the normal condition.
In some animals, such as the dog, the metcestrous period is
followed by a prolonged period of rest or ancestrum. In others,
such as the rat or the rabbit, the metcestrum may be succeeded
by only a short interval of quiescence. This short interval,
which sometimes lasts for only a few days, is called the
Dicestrum. This in turn is followed by another prooestrous
period, and so the cycle is repeated until the sexual season is
over. Such a cycle (consisting of a succession of the four periods,
prooestrum, oestrus, metoestrum, and dicsstrum) is known as
the Dices trous cycle. The number of dicestrous cycles in one
sexual season depends upon the occurrence or non-occurrence of
successful coition during oestrus. Thus, if conception takes
place during the first oestrous period of the season, there can be
no repetition of the cycle, at any rate until after parturition.
The cycle may then be repeated. If conception does not occur
at any oestrus during the sexual season, the final metoestroua
period is succeeded by a prolonged ancestrous or non-breeding
period. This is eventually followed by another prooestrum,
marking the commencement of a new sexual season. The
complete cycle of events is called the (Estrous cycle.
The number of dicestrous cycles which can occur in a female
Mammal in the absence of the male, or in the absence of successful
coition, depends upon specific and individual differences. Thus
in some animals, such as the Scotch black-faced sheep in the
1 There is evidence that "heat" may occur abnormally during gestation.
This phenomenon has been observed in dogs, cows, horses, and other
animals (see p. 51). Coition during pregnancy may result in superfoetation
(see p. 159), and may tend to occur periodically at times corresponding to
what would have been the regular heat periods if the animal had remained
non-pregnant.
2 In some animals parturition is followed almost immediately by another
prooestrum and oestrus, in spite of lactation.
38 THE PHYSIOLOGY OF REPRODUCTION
Highlands, this number is usually limited to two. In many
Rodents, on the other hand, there may be six or seven, or even
more recurrences of the cycle within the limits of a single sexual
season.
Animals in which the oestrus does not recur during the
sexual season, Heape has called Moncestrous animals. Those
in which there is a recurrence of the dicestrous cycle during a
single season, have been designated Polyoestrous animals. The
polyoestrous condition may be regarded as a device (using
teleological language) to increase the reproductive powers by
providing more frequent opportunities for successful coition.
But as to what factors are actually involved in bringing about
the rhythmic recurrence of the cycle is a question which must at
present be left open.
The differences in sexual periodicity in both monoestrous
and polycestrous Mammals, the differences in the duration of
the sexual season in polycestrous Mammals, the great variation
which occurs even in closely allied forms or even within the
limits of a single species, and the effects of domestication and
climate upon sexual and reproductive capacity are points which
will be considered in describing the various types of breeding
phenomena which exist in the different groups.
As Heape says, " the complication into which an otherwise
simple story is thrown is due ... to variation in the quiescent
period/' The two varieties of the quiescent period (anoestrum
and dioestrum) " are homologous, the one is a modification of
the other ; " and the modification is no doubt related to an
increased or decreased power of reproduction. At the same
time, for the purposes of the present chapter, " the difference
between them [must be regarded as] essential, for their relation
to the sexual season renders it necessary to discriminate clearly
between them/'
MONOTREMATA
Little is known concerning the breeding habits of the platypus
and the echidna, which represent this order, the lowest of the
Mammalia. Semon 1 states that they breed only once a year,
1 Semon, In the Australian Bush, English Edition, London, 1899. See
also Sixta, " Wie junge Ornithorfeynchi die Milch ihrer Mutter saugen,"
Zool. Anz., vol. xxii., 1899.
THE (ESTROUS CYCLE IN THE MAMMALIA 39
and that in Echidna, as a general rule, only a single egg is
impregnated and developed at a time. After the egg is laid
(for Monotremes, as is well known, differ from all other_
Mammals in being oviparous) the mother stows it away in her
pouch. This is always well developed at the sexual season,
after which it disappears, not to appear again until the ap-
proach of the next sexual season. Semon states that, although
the pouch is first visible in the embryo, it is thereafter lost to
sight until the beginning of the first procestrum.
MARSUPIALIA
It would appear probable that most Marsupials breed once
annually, but some are said to do so more frequently. Semon l
says that in the native Australian " bear " (Phascolarctus
cinereus), on the Burnett, the sexual season begins at the end
of October. Since he failed to find pregnant females until
the middle or end of November, it would seem that the
sexual season probably extends for three or four weeks. The
males at this time experience a rutting season, during which
they cry loudly, more frequently in the evening and night, but
also during the day. The gestation, as in all Marsupials, is
extremely short, the young being transferred at a very early
stage of development to the mother's pouch, as in the case of
Echidna.2
The kangaroos in the Zoological Society's Gardens in London
are stated to display sexual excitement in September, and also
in April. At such times a slight flow of mucus, which may be
tinged with a little blood, has been observed passing from the
aperture of the vagina.3 It would appear, therefore, that
kangaroos may breed twice a year. Unfortunately, there is no
positive information available as to whether oestrus recurs
during the same sexual season.
1 Semon, loc. cit.
2 In the bandicoot (Peramdes) the young are nourished by an allantoic
placenta as in the higher Mammals. (See p. 384.) This is exceptional among
Marsupials.
3 Wiltshire, " The Comparative Physiology of Menstruation," Brit. Med.
Jour., 1883.
40 THE PHYSIOLOGY OF REPRODUCTION
RODENTIA
There can be little doubt that the great majority of Rodents
are polyoestrous. Most of them, so far as is known, have
one annual breeding season, which may, under favourable
conditions, extend over several months. Thus the rat (Mm
decumanus) and mouse (M. musculus) are known to experience
a recurrence of the dicestrous cycle in the absence of the male,
while, if pregnancy occurs, a new " heat " period very rapidly
succeeds parturition. In a state of semi-domestication M. rattus
and M. decumanus have, in my experience, a fairly regular breed-
ing season from about the end of January until the end of May.
During this period the majority of mature females are either
pregnant or suckling their young (that is, of course, among
females which have been allowed to run freely with males).
Pregnancy may occur -at other times of the year, but is not
nearly so common. The duration of the dioestrous cycle in the
rat is said to be about ten days ; l the period of gestation is
approximately three weeks. Heape states that M . minutus and
M. sylvaticus are also probably polyoestrous. The bank vole
(Arvicola glareolus) is almost certainly polycestrous, since it can
become pregnant immediately after parturition at certain times
of the year. The same condition no doubt exists in the field vole
(A. agrestis), which breeds in Britain from January to October.2
According to Lataste,3 Eliomys quercinus, Gerbillus hertipes,
Dipodillus campestris, D. simoni, Meriones shaivi, and M. longi-
frons are also polycestrous. The length of the dicestrous cycle
in all these animals, as observed by the same investigator, is
usually about ten days, as in the common rat.
In the wild condition in Britain, according to Heape, re-
current dicestrous cycles last " about three months, probably, in
Arvicola agrestis ; from four to six months, probably, in Mm
minutus ; about nine months in Mus rattus ; and even longer,
perhaps, in Mus musculus and M. decumanus." From my own
experience with the two latter species in captivity, I am disposed
1 Heape, loc. cit.
2 Millais, British Mammals, vol. ii., London, 1905.
3 Lataste, Recherches de Zooethique sur les Mammiferes de Vordre dcs Rongcurs,
Bordeaux, 1887.
THE CESTROUS CYCLE IN THE MAMMALIA 41
to believe that Heape has overstated the duration of the sexual
season in these animals in a state of nature.
The breeding season in the wild rabbit (Lepus cuniculus)
in this country generally lasts from about February to May,
but may be continued for longer. In the domesticated breeds
it sometimes lasts nearly the whole year if the circumstances be
favourable in regard to warmth and food supply. Heape says
that five or six months only is the usual duration of the period
during which dioestrous cycles recur in the domestic rabbit, and
that if oestrus is experienced in winter it may occur inde-
pendently of the possibility of pregnancy.
The duration of the dioestrous cycle varies considerably.
" While some individuals exhibit oestrus every three weeks
fairly regularly, others do so every ten days ; on the whole, I
think ten to fifteen days is the usual length of their dioestrous
cycle/' l In Lepus variabilis recurrent dicestrous cycles are
probably continued for about two months.
The squirrel (Sciurus vulgaris) in Britain, according to Heape,
is probably moncestrous ; but this animal, in Southern Europe
and Algiers, according to Lataste, is apparently polyoestrous.
In Britain squirrels breed early in the year, and sometimes have
a second litter in August.
It is difficult to determine the length of the procestrum and
oestrus in Rodents, since the external changes which characterise
these conditions are comparatively slight. Heape says that the
prooestrum in the rabbit lasts, probably, from one to four days.
At this time the vulva tends to become swollen and purple in
colour, but there is no external bleeding. The same may be
said of the rat and the guinea-pig ; but, in the experience of
the writer, it is generally impossible to detect the procestrous
condition in either of these animals with absolute certainty.
(Estrus probably lasts for about a day. Lataste 2 states
that external bleeding occurs during the " heat " periods
of Pachyuromys duprasi, Dipodillus simoni, and Meriones
shawi.
The guinea-pig (Cavia porcellus) in captivity can become
pregnant at any season, but more frequently in the summer
than in the winter. " Heat " rapidly succeeds parturition, as
1 Heape, loc. cit. 2 Lataste, loc. cit.
42 THE PHYSIOLOGY OF REPRODUCTION
in the case of so many other Rodents.1 The period of gestation
is about sixty-two days, an unusually long time for so small an
animal, being more than twice as long as the gestation period of
the rabbit. As a result the newly born guinea-pig is well
advanced in development, and able to feed for itself, instead
of being dependent on its mother's milk.
In most male Rodents the testes undergo a periodic increase
in size and descend into the sessile scrotum at the beginning
of the season of rut, after which they become smaller again, and
are withdrawn into the peritoneal cavity. In the Leporidae,
however, and in some other species, the testes are not so re-
tracted, but remain throughout the year in the scrotal sacs.2
UNGULATA
This order contains several examples of animals which are
almost certainly monoestrous in a state of nature, but are
polyoestrous in captivity or under domestication. In the latter
case the increase in sexual capacity appears to be due partly to
the inherited effects of domestication, and partly to the direct
influence of a more favourable environment.
For example, the sheep presents a complete gradation from
the apparently monoestrous condition of some wild species to
the extreme degree of polyoestrum, which is reached by certain
of the more domesticated breeds.3
The Barbary wild sheep (Ovis tragelaphus) in the Zoological
Society's Gardens is moncestrous, breeding only once annually.4
The same is stated to be the case with the Burrhel sheep
(0. burrhel), although the moufflon (0. musimon) in captivity may
experience two or more recurrent dioestrous cycles in an annual
sexual season.5 It would seem, however, from the account
given by Lydekker 6 of the breeding habits of 0. musimon, as
1 Sobotta, " tiber die Bildung des Corpus Luteum beim Meerschweinchen/'
Anat. Hefte, vol. xxxii., 1906.
2 Owen, On the Anatomy of Vertebrates, vol. iii., London, 1868.
3 Marshall, "The CEstrous Cycle, &c., in the Sheep," Phil. Trans. £.,
vol. cxcvi., 1903.
4 Heape, loc. cit.
5 I am indebted to Mr. F. E. Beddard, Prosector of the Zoological Society,
for this information.
6 Lydekker, Wild Oxen, Sheep, and Goats of All Lands, London, 1898.
THE (ESTROUS CYCLE IN THE MAMMALIA 43
well as 0. vignei, 0. ammon, and 0. canadensis, that these sheep
in their wild condition are probably monoestrous, for their
annual sexual season is of short duration, and occurs with
great regularity. Similarly it may be inferred from Prjewalsky's
statements l that 0. poli, 0. burrhel, and 0. argali are monoestrous
and breed once a year. Among wild sheep generally the sexual
season occurs as a rule in autumn, but it may vary with the
locality or climate. Thus with 0. vignei in the Punjab, the
sheep begin to breed in September, whereas, with the same species
in Astor, the sexual season must be considerably later, since the
young in the latter district are produced about the beginning of
June.2
Scotch black-faced sheep in the Highlands experience two
dices trous cycles, each of three weeks' duration, so that the
annual sexual season for these animals lasts six weeks. In the
Lowlands the sheep of this breed may have at least three re-
current dicestrous cycles in the absence of the ram, while flock-
masters inform me that, under unusually favourable conditions,
there may be as many as five or six, the duration of each cycle
varying from about thirteen to eighteen days. It can hardly
be doubted that of the two conditions of the Scotch black-
faced sheep that of the Highland ewes is the more natural, for
sheep, in their wild state, are essentially mountain animals,
being almost entirely confined to mountain districts in the
Holarctic region, their range only just extending across the
border into the far warmer Oriental region. " The immense
mountain ranges of Central Asia, the Pamir, and Thian-Shan
of Turkestan may be looked upon as the centre of their
habitat." 3
The sexual season in hill sheep in Great Britain is ordinarily
from about the middle of November until the end of the year.
Under exceptional circumstances individuals may experience
oestrus at other seasons, such as in April after an early abortion
in the winter. In other British breeds the sexual season is
earlier. Thus Hampshire Down sheep are often " tupped " in
1 Prjewalsky, Mongolia, the Tanyut Country, and the Solitudes of Northern
Tibet (Morgan's Translation), London, 1876.
2 Lydekker, loc. cit.
3 Flower and Lydekker, Mammals Liviny and Extinct, London, 1891.
44 THE PHYSIOLOGY OF REPRODUCTION
the summer, but they do not, as a rule, breed more than once a
year. The Limestone sheep of Westmorland and Derbyshire,
and the Dorset Horn sheep of the South of England, are the only
British sheep which are ordinarily capable of breeding more
than once annually. With the former the general lambing
season is from the middle of February to the middle of March,
but lambs are often born earlier. The ewes sometimes receive
the ram very early when suckling the lambs, so that a second
crop of lambs is born in August. This increase in the sexual
capacity is especially noteworthy in view of the fact that Lime-
stone sheep are classed as a mountain breed which thrives best
on dry heaths or bare hill pastures. In Dorset Horn sheep
lambs are frequently produced twice a year, but the practice is
discouraged as it is said to deteriorate the ewes. With this
breed oestrus may continue to recur (in the absence of the ram)
from the autumn sexual season (when the sheep are ordinarily
tupped) onwards until the following spring.
With many foreign breeds lambs are born twice yearly.
Thus Mr. Annandale informs me that the horned sheep which
run half wild in Patani, in the Malay Peninsula, normally have
lambs twice a year. It would appear also that among the
indigenous sheep of India, which are scarcely ever supplied
with any artificial or other food, green or dry, beyond what they
can pick up at the pasture ground, lambs may be born three
times in two years, and that there are no definite seasons for
lambing.1
Among the Merino sheep in Cape Colony the sexual season is
April (the autumn month, corresponding to October in this
country), but some sheep come " in season " earlier. At high
altitudes, however, where the sheep subsist entirely upon the
natural produce of the veldt, the sexual season is May, or a
month later than the usual time in Cape Colony. On the other
hand, in the low country below the second range of mountains,
there are two seasons for " tupping/' and lambs are produced
twice a year. Among the Merinos in Argentina there are also
two breeding seasons within the year.
Probably the maximum amount of sexual activity experi-
1 Shortt, A Manual of Indian Cattle and Sheep, 3rd Edition, Madras,
1889.
THE CESTROUS CYCLE IN THE MAMMALIA 45
enced by any sheep is that reached by certain Australian
Merinos which are described as being able to breed all the
year round, a fact which implies, in the absence of gestation,
an unbroken series of dioestrous cycles. The report of the
Chief Inspector of Stock for New South Wales divides the
time of lambing into six periods which embrace the entire
year.1
That the great variability in sexual activity which the sheep
exhibits is dependent largely upon differences in food supply
and climate cannot be doubted, for the black-faced sheep in
Scotland, and the Merinos in Cape Colony afford direct evidence
that this is the case. Indeed, the effect of the environment on
the recurrence of breeding was noted long ago by Aristotle,2 who
observes that " in some places where the weather is warm and
fine, and food is abundant/' sheep may have lambs twice a
year. The result of flushing (or the practice of stimulating
the generative system by supplying extra food or better pasture,
and thereby hastening the approach of the sexual season and
increasing the fertility) is further evidence of the effect of good
nourishment upon the sexual and reproductive powers. On
the other hand, there can be no question that the varying degrees
of breeding activity are in part racial characteristics, as is shown,
for example, by the Dorset Horn sheep in the south of England,
and still more evidently by the Limestone sheep of Westmor-
land and Derbyshire. But that an increase in the duration (or
more frequent recurrence) of the sexual season is not necessarily
a highly artificial condition or the result of special attention in
regard to food supply, &c., on the part of the flock-master, is
shown by such a condition occurring among the indigenous
sheep of India and the half-wild sheep of Patani.
The duration of the dioestrous cycle in black-faced sheep,
as already mentioned, is from about thirteen to twenty-one
days, the variation appearing to depend partly upon the nature
of the country in which they live. In other breeds the cycle may
be said to vary within approximately the same limits. Ellen-
1 Wallace (R), Farming Industries of Cape Colony, London, 1876 ; The Rural
Economy and Agriculture of Australia and Neiv Zealand, London, 1891 ;
Argentine Shoivs and Live Stock, Edinburgh, 1904.
2 Aristotle, History of Animals (Crosswell's Translation), Bonn's Library,
London, 1862.
46 THE PHYSIOLOGY OF REPRODUCTION
berger,1 however, gives from twenty to thirty days as the length
of this interval. The prooestrum and oestrus together do not
as a rule occupy more than two or three days, and oestrus alone
may last for only a few hours. The external signs of the
prooestrum are comparatively slight in sheep. The vulva is
usually somewhat congested, and there is often a flow of mucus
from the external generative aperture, but blood is seldom
seen. Owing to the extreme shortness of the " heat " period the
mucous flow may continue during the oestrous and metoestrous
periods. The internal changes are briefly described in the
succeeding chapter. The only external indication of oestrus is
that afforded by the behaviour of the ewes. At this time they
tend to follow the ram, and display a general restlessness of
demeanour. The period of gestation is twenty-one or twenty-
two weeks. Nathusius' observations show that it is fairly
constant within the limits of particular breeds.2
The oestrous cycle in the sheep, and its great variability,
have been discussed at some length, since this animal is pro-
bably typical of most Ungulata in the way in which its generative
system is affected by different conditions of life, while the facts
about other Ungulates are not so perfectly known. The effect
of changed conditions upon the sheep's fertility, i.e. upon its
capacity to bear young (as distinguished from mere sexual
capacity), is a subject which is dealt with more fully in a future
chapter (Chapter XIV.).
The wild goat, like the wild sheep, has a very restricted
sexual season,3 while, according to Low, the domesticated goat
experiences oestrus at very frequent periods.4
A similar statement may be made about cattle, for Heape 5
says that, whereas wild cattle in captivity are capable of re-
production at any time of the year, and experience a remark-
able increase in the recurrence of their dioestrous cycles, we
are led to infer from the limited calving season among
1 Ellenberger, Veryleichende Physiologic der Haussaiiyethiere, vol. ii. Berlin,
1892.
2 Nathusius, " Ueber einen auffallenden Racenunterschied in der Trachtig-
keitsdauer der Schafe," Zool. Garten, Jahrg. 3, 1862.
3 Lydekker, loc. cit.
4 Low, The Domesticated Animals, London, 1845.
5 Heape, loc. cit.
THE CESTROUS CYCLE IN THE MAMMALIA 47
similar animals in the wild state that the sexual periods
are likewise restricted. Raciborsky l says that in the more
domestic types of cattle the cows receive the bull more
frequently than in the wilder breeds. Ellenberger 2 states that
among domestic cattle the dicestrous cycle varies from about
two to four weeks, but Schmidt 3 has shown that the differences
may be much greater. Wallace 4 says that oestrus recurs in
summer every nineteenth day, but in winter it may not recur
oftener than every twentieth or every twenty-first day. Usually
the cow seeks the bull again four or five weeks after calving.
Shortt,5 however, states that in India this does not occur until
after six or nine months. Blood is not infrequent in the ex-
ternal procestrous discharge of cows and heifers. Emrys-Roberts6
has described the internal generative organs of a prooestrous
cow as containing a watery secretion tinged with blood. The
secretion was found to contain far less mucin than during the
ancestrous period.7
The period of gestation in cattle is about nine months, but
it is slightly variable.
According to Heape, who has collected evidence from various
authorities, the ibex, markhor, barasingha, and Hemitragus
jemlaicus in Cashmir, as well as the American bison, black-
tailed deer in Montana, red-deer, fallow-deer, and roe-deer,8 and
1 Raciborsky, Traite de Menstruation, Paris.
2 Ellenberger, loc. cit.
3 Schmidt, " Beitriige zur Physiologie der Brunst beim Rinde," Disserta-
tion, Zurich, Miinchen, 1902.
4 Wallace (R.), loc. cit.
5 Shortt, A Manual of Indian Cattle and Sheep, 3rd Edition, Madras,
1889.
6 Emrys-Roberts, " A Further Note on the Nutrition of the Early Embryo,
&c.," Proc. Roy. Soc. B., vol. Ixxx., 1908.
7 According to Emrys-Roberts, the profuse mucinous secretion during the
prooestrum in the Mammalia is derived, not from the body of the uterus,
but from the cervix and vagina.
8 There has been some controversy regarding the breeding season and
period of gestation in roe-deer. According to Bischoff (Entivicklungsgeschichte
de.s Rehcs, Giessen, 1854) rut occurs in early autumn, but the embryo is not
developed beyond the stage of segmentation in the following spring. Groh-
mann (Sport in the Alps, Edinburgh, 1904) says that rut is experienced in
July and the beginning of August, but that there is a "false rut" in
November. Observations on roe-deer in Vienna showed that the period
of gestation is ten months ; for seven females which were served by one
48 THE PHYSIOLOGY OF REPRODUCTION
several antelopes are all probably monoestrous in the wild state.
This is rendered not unlikely from the limited sexual and calving
seasons which these animals are known to experience, but it is
by no means certain. " The American bison experiences a
sexual season from some time in July until some time in August.
[Catlin says August and September are the months when they
breed ; see below.] In the Cashmir ibex it persists during
parts of November and December. In the markhor and
Hemitragus jerulaicus in Cashmir it occurs in December, while
in the barasingha in that country, from September 20th to
November 20th, it has been observed. ... In Scotland the red-
deer's sexual season lasts three weeks, during September and
October, according to Cameron ; 1 while in this country [England]
September is the sexual month for the fallow-deer,2 and July
and August the time when the roe-deer will receive the male.
" In all these cases there can be little over three weeks
during which copulation takes place, and the extremely limited
period during which parturition occurs strongly corroborates
the view that this is the extent of the usual time during which
sexual intercourse is possible. The fact that in captivity three
weeks is the usual period which intervenes between two oestri
in such animals, and the extreme probability that individual
females do not experience oestrus at exactly the same time,
predispose one to believe that they are moncestrous in the wild
buck in July 1862, gave birth each to two young in the following May. It
would appear probable, therefore, that the ovum lies dormant during the
early months of gestation. Grohmann suggests that the " false rut " in
November may have a quickening influence on the ovum, and so cause it
to develop.
1 Millais says (vol. iii. 1906) that the actual time of rut depends much on
the season. September 28, in Scotland, is called " the day of roaring." Sir
S. M. Wilson (Field, October 8, 1904), however, reports a case of a stag which
roared during the whole summer in Kinveachy Forest, Boat of Garten, in
1904. Stags eat little or nothing during the rutting season, and lose weight
rapidly. During the first days of roaring they are said to suck up a mixture
of peat and water (Millais, loc cit ).
2 Millais says (loc. cit ) that the fallow-deer in England ruts in October.
The necks of the big bucks swell greatly during the first week, and the
animals become more and more unsettled until about the 25th, when the first
calls are heard. The actual rut is short as a rule. The doe drops her calf
about the beginning of June, and rarely two or three are born at a time.
Sometimes, however, the females may come in season at irregular times, and
drop calves in any of the months after June and even as late as November.
THE (ESTROUS CYCLE IN THE MAMMALIA 49
state ; but, if the limit of time for coition is three weeks, there
is still just time for the females to undergo two dioestrous cycles,
and it is this possibility which prevents positive assertion on
the matter.
" Among captive animals, not more than two dioestrous
cycles have been observed in the gnu during one sexual season.
Gazella dorcas has two or three ; the giraffe about three ; while
the eland, nylghau, and water-buck have a series of dicestrous
cycles, each lasting three weeks, during May, June, and July
each year.
" The gayal and bison, the axis and wapiti deer, on the other
hand, experience a continuous series of dicestrous cycles all the
year round, at intervals of about three weeks. " l
Heape states also that with red-deer in the Zoological
Gardens there is a very extensive series of dioestrous cycles,
and that with wapiti deer in captivity the possibility of
pregnancy at any season is only prevented by the fact that
the male does not rut during the casting and growth of the
antlers.
The males of many of the other species referred to experience
a definite rutting season, like the stag in Britain.
As already mentioned, the male camels in the Zoological
Gardens in London experience rut in early spring, or at the
same time as the sexual season of the female camels in Mongolia.
The period of gestation in the camel is thirteen months, so that
in this animal, as in the walrus among carnivores, the recurrence
of the sexual season is delayed by pregnancy, and conception
cannot take place oftener than once in two years.2 The same
is the case with the wild yak in the deserts of Tibet,3 and also,
in all probability, with the musk-ox in Greenland.4
The sexual season in many Ruminants is a period of in-
tense excitement, especially in those cases in which the males
experience a definite rut. (See above, p. 27, in Chapter I.)
Thus, Catlin,5 referring to the American bisons, says : " The
running season, which is in August and September, is the time
1 Heape, loc. cit.
2 Swayne, Seventeen Trips through Somaliland, London, 1895.
3 Prjewalsky, loc. cit. 4 Lydekker, loc. cit.
5 Catlin, North American Indians, vol. i., 2nd Edition, London, 1841.
D
50 THE PHYSIOLOGY OF REPRODUCTION
when they congregate into such masses in some places as
literally to blacken the prairies for miles together. It is no
uncommon thing at this season, at these gatherings, to see
several thousands in a mass, eddying and wheeling about under
a cloud of dust, which is raised by the bulls as they are pawing
in the dirt or engaged in desperate combats, as they constantly
are, plunging and butting at each other in the most furious
manner. In these scenes, the males are continually following
the females, and the whole mass are in a constant motion ;
and all bellowing (or ' roaring ') in deep and hollow sounds
which, mingled together, seem, at the distance of a mile or two,
like the noise of distant thunder."
That the antlers are the fighting weapons in stags, and that
their growth is associated with the advent of the sexual season,
after which time they are cast off, are facts which have been
already referred to. The effects of castration upon the growth
of the antlers are described in a later chapter (p. 305).
Passing to the non-ruminating Ungulata, we find that the
wild sow has only one annual sexual season. It is not certain
whether this consists of more than a single cestrous cycle. Under
domestication, however, the sow is polycestrous, and may take
the boar five weeks after parturition. The duration of the
dicestrous cycle is from two to four weeks, according to Fleming.1
The period of gestation is about four months. Litters are
usually produced only in spring and autumn ; but by weaning
the young early (or partially weaning them), and feeding the
mother liberally, it is possible to get five litters in two years.
A sanguineo-mucous flow has been observed issuing from the
genital aperture during the procestrum. At the same time
the vulva is distinctly swollen.
Wiltshire 2 states that in the hippopotamus in captivity a
condition of oestrus may be experienced at regular monthly
intervals. This animal has been known to breed in Zoological
Gardens.
The mare is polyoestrous, the normal dicestrous cycle being
about three weeks and the cestrous period a week, though its
1 Fleming, Veterinary Obstetrics, London, 1878.
2 Wiltshire, loc. tit. See also Ellenberger, loc. tit., and Wallace (R.),
Farm Live-Stock of Great Britain, 4th Edition London 1907.
THE CESTROUS CYCLE IN THE MAMMALIA 51
actual length may vary by three or four days.1 The sexual
season in the absence of the stallion extends throughout- the
spring and early summer months, and is generally longest in
the more domesticated breeds. Professor Ewart informs me
that in a pony imported from Timor, which is in the Southern
Hemisphere, oestrus was experienced in the autumn, or at the
same time as the spring in Timor (cf. camels, p. 49). The
period of gestation in the mare is eleven months, and " heat "
recurs eleven days after parturition. This is called the " foal
heat/' Certain mares are irregular in the recurrence of the
" heat " periods, and, in some, " foal heat " does not occur until
seventeen days after parturition instead of the usual eleven
days. In exceptional cases a mare, like a cow, may conceive
at the " foal heat " and yet take the horse three weeks later,
just as though she had failed to become pregnant.2 Heape
states that, very exceptionally, mares are moncestrous. Blood
has been observed in the mare's procestrous discharge, but it is
not generally present. The genitalia, however, are always
swollen and congested, and a glutinous secretion is generally
emitted from them. The clitoris and vulva often undergo a
succession of spasmodic movements, preceded by the discharge
of small quantities of urine. Suckling mares tend to fail in
their milk supply, and the quality of the milk appears to undergo
some kind of change, as it is frequently the case that foals
during the heat periods of their dams suffer from relaxation of
the bowels or even acute diarrhoea. In mares which are not
suckling the mammary gland becomes congested and increases
in size during the heat. At the same time some mares de-
velop great excitability, and kick and squeal, becoming dangerous
to approach and impossible to drive. There is, however, great
variation, for other animals may pass through the " heat "
period without exhibiting any well-marked signs of their con-
dition, which in a few instances can only be determined by the
behaviour of the mare towards the stallion.3
1 Ewart found that in Equus prjewalsky, oestrus lasted a week.
2 Wallace, loc. cit. Professor Ewart informs me that pregnant mares do
not necessarily abort as a result of taking the horse at the third, sixth, or
even ninth week of gestation.
3 Wortley Axe, "The Mare and the Foal," Jour, of the Royal Agric. Soc.,
3rd Series vol. ix., 1898. Ewart ("The Development of the Horse," to be
52 THE PHYSIOLOGY OF REPRODUCTION
The elephant in captivity is said to be polyoestrous, but I
can find no record of the duration of the dices trous cycle. Since
pregnancy is very prolonged (twenty months), the sexual
season cannot occur more than once in two years ; that is, if
the animals breed. The elephant in the Zoological Gardens in
London is stated to have persistent oestrus probably for three
or four days.
CETACEA
Little is definitely known about the periodicity of breeding
in Cetacea. According to Millais,1 the right whale brings forth
in March in every other year, the young being suckled for about
twelve months. The humpbacked whales, blue whales, and
sperm whales appear to have no regular time for breeding, but
Millais says the young of the humpbacked whales are generally
born sometime during the summer. Haldane's records,2 which
appear to refer to several different whales, show that foetuses
varying in length from six inches to sixteen feet were found
in animals captured at the Scottish whaling stations in the
summer of 1904. This great variation seems to imply that there
is no regular season at which whales copulate, and that very
possibly these animals are poly ces trous. Lillie 3 states that two
specimens of Balcenoptera musculus were taken off the west of
Ireland on July 31, 1909, and that one contained a foetus of one
foot in length, while the other had a foetus of five and a half feet
in length. Lillie says also that several female rorquals having
foetuses of different sizes were captured within a short time of
published in Quar. Jour. Micr. Science, says that the period of oestrus in mares
tends to be shorter the later in the season, and when the food becomes less
plentiful and less nutritious all external signs of oestrus disappear. Under
favourable conditions, however, mares may become pregnant in winter.
Ewart gives the following as the periods of gestation in various Equidae : —
Asses and zebras, 358 to 385 days ; Prjewalsky's horse, 356 to 359 days ;
Celtic pony, 334 to 338 days. In coarse-headed types of horse it is about the
same as in Prjewalsky's horse, but in the finer breeds the period is the same
as in the Celtic pony. In abnormal cases pregnancy may be unduly pro-
longed in mares as in other animals, a mare occasionally going twelve months
in foal instead of eleven.
1 Millais, The Mammals of Great Britain, vol. iii., London, 1906.
2 Haldane, "Whaling," &c., Annals of Scottish Nat. Hist., April, 1905.
3 Lillie, " Observations on the Anatomy and General Biology of some
Members of the larger Cetacea," MS. still unpublished.
THE (ESTROUS CYCLE IN THE MAMMALIA 53
one another. These observations, therefore, are in a general
way confirmatory of those of Haldane.
According to Guldberg and Nansen,1 the porpoise copulates
at any time between June and October, the period of gestation
being ten months or longer. The white-sided dolphin is said
to copulate in late summer, pregnancy being about ten months,
and the white-beaked dolphin is thought to be similar.2
Humpbacked whales and other Cetacea have been described
as indulging in amorous antics at the breeding time, rubbing
against one another and patting one another with their long
fins.3
CARNIVORA
In the female of the dog the average duration of the complete
oestrous cycle is six months, there being two annual " heat "
periods, typically in the spring and in the autumn. It
follows, therefore, that the bitch is moncestrous. Bitches be-
longing to the smaller breeds tend to come " on heat " more
frequently than those of the larger varieties. Thus, in Irish
terriers, the cycle may recur after four months, though in this
breed six months is the more ordinary time.4 On the other
hand, in Great Danes the duration of the cestrous cycle is often
as* much as eight months. It would appear that in those cases
where " heat " recurs as often as every four months, this is
only when pregnancy is prevented, for more than two litters of
pups are seldom if ever produced in a year.' Stonehenge 5 says
that there is much individual variability in the periodicity of
the cycle, and that " heat " may recur at any interval from
four up to eleven months, but that six, five, and four months
are the most usual periods. Each bitch as a rule has her own
peculiar period to which she remains constant, unless systema-
tically prevented from breeding, in which case the periods tend
to recur irregularly or even cease altogether.6 It has been
observed also that the recurrence of the sexual season tends to
1 Guldberg and Nansen, "On the Structure and Development of the
Whale," Bergen, 1904.
2 Millais, loc. cit. 3 Ibid.
4 Marshall and Jolly, loc. cit.
5 Stonehenge, The Dog in Health and Disease, 4th Edition, London,
1887. 6 Heape, loc. cit.
54 THE PHYSIOLOGY OF REPRODUCTION
become irregular with advancing age, and this irrespectively of
whether or not the animal is permitted to become pregnant. The
periodicity depends also to some extent upon climate, for in
Danish Greenland the dogs usually breed only once a year.1
The procestrum in the bitch is characterised externally by the
vulva being swollen and moistened with mucus, and by the
existence, usually, but not absolutely invariably, of a flow of
blood from the aperture of the vagina. The length of the
procestrum is about ten days. The sanguineous discharge
generally ceases at the commencement of oestrus, which may
last for another week or ten days.
Heape states that the winter oestrus in some breeds does not
last so long as the summer oestrus. In certain individuals a
relatively slight mucous or sanguineo-mucous flow takes place
during the period of oestrus, and may even be continued beyond
it, but this is exceptional. Stonehenge states that a bitch will
not, as a rule, receive the dog until external bleeding has sub-
sided, and that the most favourable time for successful coition
is about the eleventh day of " heat " (in other words, at the
beginning of the period of oestrus). This statement is fully
borne out by dog-breeders.
The external changes which occur during " heat " are
accompanied by changes in the metabolism, for Potthast,2
working on the nitrogen metabolism of the bitch, records a
slight retention of nitrogen during the " heat " period. A
similar result was obtained by Hagemann,3 who states that the
retention is followed by a loss of nitrogen after copulation.
These results should be compared with those recorded for
menstruating women (see p. 68).
The histological changes which take place in the uterus
during the cestrous cycle are described in the next chapter.
The period of gestation in the dog varies from fifty-nine to
sixty-three days. With dogs belonging to the smaller breeds
the period is often somewhat less than with large dogs. The
1 Rink, Danish Greenland, London, 1877.
2 Potthast, " Kenntniss des Eiweissumsatzes," Dissertation, Leipzig,
1887.
3 Hagemann, " Eiweissumsatz im tierisch Organism us," Dissertation,
Erlangen, 1891. Cf. also Schorndorff, " Einfluss der Schilddruse auf den
Stoffwechsel," Pfliiger's Arch., vol. Ixvii., 1897.
THE (ESTROUS CYCLE LN THE MAMMALIA 55
period of lactation is very variable in duration, and may extend
until the commencement of the next procestrum.
The wild dog of South America (Canis azarce), according to
Rengger,1 breeds only in winter, and therefore but once a
year. The same is said to be the case with the wolf and the
fox in their wild state ; but these animals, in the Zoological
Gardens in London, experience two annual " heat " periods
like the dog.2 The wolves in the Dublin Gardens, how-
ever, are stated to have only one annual sexual season
when permitted to breed ; otherwise they come " in heat "
more frequently, but are always monoestrous.3 The period of
gestation in the wolf and fox is approximately the same as in
the dog, i.e. about two calendar months.
Bischoff 4 refers to the fact that the sexual season of the
fox is affected by the nature of the country which it inhabits,
foxes which live at high altitudes breeding later than those
residing on the plains. Millais 5 says that fox-cubs in most
parts of Britain are not born until the end of March or beginning
of April, whereas, in the south of England, they are often pro-
duced as early as January.
The Cape hunting-dog (Lycaon pictus) has been known to
have bred in captivity on several occasions, and notably in the
Gardens at Dublin, where six litters were produced from a
single pair between January 1896 and January 1900. The
first three litters were born in January, the fourth in November
1898, the fifth in May 1899, and the sixth in January 1900.
Cunningham writes : " It is not easy to offer a satisfactory
explanation of the irregularity of the fourth and fifth litters.
1^ am inclined to believe, however, in the absence of definite
information on this point obtained from the animals in a state
of nature, that the lycaon breeds only once a year, and that
the irregularity noticeable in the fourth and fifth litters is due
1 Rengger, Naturgeschichte d. Saugethiere von Paraguay, Basel, 1830.
2 Heape, loc. cit.
3 For the information regarding the breeding of the animals in the Royal
Zoological Society's Gardens, Dublin, I am indebted to the late Professor D. J.
Cunningham and Dr. R. F. Scharf. (See Marshall and Jolly, loc. cit.)
4 Bischoff, " Ueber die Rauhzeit des Fuchses und die erste Entwicklung
seines Eies " Sitz. der Math.-phys., Wien, Clause vom 13 Jmii, vol. ii., 1863.
5 Millais, loc. cit.
56 THE PHYSIOLOGY OF REPRODUCTION
to a tendency on the part of the Dublin specimens to adapt
themselves to the climatic conditions of Ireland. At the same
time it should be mentioned that certain indications were ob-
served in connection with the demeanour of the parents towards
each other which seemed to indicate that the sexual instinct
was excited at more than one period of the year." The period
of gestation was ascertained to be about eighty days, or nearly
three weeks longer than in the domestic dog. " As might be ex-
pected, the young when they are born are more lusty and more
advanced in development than new-born puppies of the dog."
On one occasion, when the litter produced was unusually large,
the gestation period was lengthened to eighty-six days.1
The female of the domestic cat generally breeds two or
three times a year. According to Spallanzani 2 the " heat "
periods occur in February, June, and October, but there can
be no doubt that many individuals breed at other times, and
that there is great variation.3 Heape 4 says that there may be
no less than four sexual seasons within a year, but this can
only be when the cats are not allowed to become pregnant.
The usual number of litters, in my experience, is two, in typical
cases in spring and autumn as in the dog. Heape states also
that feral cats breed only once a year. The domestic cat is
polycestrous, and may experience a long succession of dicestrous
cycles in one sexual season, each dicestrous cycle lasting about
fourteen days and sometimes less.5 The period of gestation is
about nine weeks.
Millais 6 says it is uncertain whether the wild cat has one
1 Cunningham (D. J.)» " Cape Hunting Dogs (Lycaon pictus) in the Gardens
of the Koyal Zoological Society of Ireland," Proc. Roy. Soc. JEdin., vol. xxv. ,
1905.
2 Spallanzani, Dissertations, vol. ii., London, 1784.
3 Marshall and Jolly, loc. cit. I have known a cat experience oestrus
regularly at intervals of about a fortnight from December until the following
August, but such a long succession of dioestrous cycles is probably unusual.
4 Heape, loc. cit.
5 Heape, loc. cit. Mr. W. O. Backhouse informs me that in his experience
with Siamese cats the females, if the kittens are destroyed or birth is
premature, come on heat regularly about eight days after parturition. This
probably occurs in other breeds, at any rate in spring and summer.
6 I am much indebted to Mr. A. H. Cocks for supplying me with interest-
ing information concerning various Carnivora in captivity.
THE CESTROUS CYCLE IN THE MAMMALIA 57
or two annual breeding seasons. The probability is that there
is only one (in March), the young being born in May ; but Millais
records that he has seen young wild cats, which could not have
been more than forty days old, killed in Scotland in October.
Cocks, in a letter quoted by Millais, says that he has received
wild cats which, judging from their size, were probably born in
August or September, and that in captivity he has observed a
female experience " heat " during the summer. " Many years,
when owing to the death of the young, or the fact that the pair
had not bred together in the spring, I have kept male and
female together all summer, but they showed no inclination to
breed/' In a more recent letter to the author Mr. Cocks states
that the old female wild cat in his possession came " in season "
and received the male in the autumn of 1904, after the death
of the kittens which were born earlier in the same year. The
animal, however, failed to become pregnant. In the experience
of this observer the commonest month for wild kittens is May,
but the range of dates in his collection varies from April 20
to July 22. The period of gestation was ascertained to be
sixty-eight days. The period of oestrus was observed to last for
five days, or about the same time as in the domestic cat.
The male wild cat has a definite season of rut (like the stag),
and calls loudly and incessantly, making far more noise than
the female cat.1 This information is interesting, since the
males of most Carnivora, so far as is known, do not experience
anything of the nature of a recurrent rutting season, although
many individuals show indication of increased sexual activity
at some times more than at others. So far as I am aware,
nothing of the nature of a rutting season is ever known in the
males of the domestic cat, dog, or ferret, all of which seem to
be capable of coition at any period of the year. On the other
hand, the males of certain seals appear to possess a season of
rut at the same time as the sexual season in the females.
Little is known definitely regarding the breeding habits of
the larger Felidae in their wild state, beyond the fact that they
probably agree in having a single annual sexual season. In
captivity certain of them, at any rate, are polyosstrous. Thus,
1 I am indebted to Mr. Cocks for information regarding the breeding
habits of the wild cat.
58 THE PHYSIOLOGY OF REPRODUCTION
in the lioness oestrus has been known to recur at intervals of
three weeks until the animal became pregnant, while the period
of oestrus may itself last a week.1 Further, the lioness may
experience three or four sexual seasons in the year, as in the
domestic cat, this having been observed to occur in the lioness
in the Dublin Zoological Gardens when copulation had not
been successful, or when the animals were not permitted to
breed. If allowed to become pregnant the lioness at Dublin
may still experience two sexual seasons, and have two litters of
cubs within the year. The puma in the Dublin Gardens is
stated to have one sexual season annually if breeding, or two
if there is no gestation. The larger Felida? as a rule breed com-
paratively freely in confinement, some places, such as the
Dublin Gardens, being famous for successful lion breeding. The
period of gestation in the lioness is from fifteen to sixteen weeks ;
that of the tigress is about twenty-two weeks ; while the puma
goes with young for fifteen weeks.
Most species of bears, both in their wild state and in confine-
ment, are moncestrous and have one annual sexual season. The
grizzly bear, however, according to Somerset,2 bears young only
once in two years. The bears in the Zoological Gardens at
Dublin, on the other hand, may experience more ' than one
annual sexual season if pregnancy does not occur. The period
of gestation in the brown bear is seven months ; in the grizzly
bear it is probably longer. Heape states that with the bears in
the Zoological Gardens in London oestrus may be experienced
for two or three months continuously ; but this condition, as he
points out, is unnatural and probably an effect of confinement,
for though coition can occur, it does not, as a rule, result in
pregnancy.
The ferret, which is a domesticated variety of the polecat,
is moncestrous, but may have as many as three annual sexual
seasons,3 which, however, instead of being distributed at regular
intervals throughout the year, occur only in the spring and
summer, the autumn and winter being occupied usually by a
prolonged anoestrous period. This tendency towards a con-
1 See Marshall and Jolly, loc. cit.
2 Somerset. Quoted by Heape, loc. cit.
3. Carnegie, Ferrets and Ferreting, London.
THE (ESTROUS CYCLE IN THE MAMMALIA 59
centration of sexual seasons during one part of the year may
be considered as an approach to a condition of polycestrum ;
for, if the oestrous periods were to recur at still shorter intervals
than is actually the case, they could be regarded as forming so
many dicestrous cycles in one sexual season. So far as I am
aware, the ferret does not experience oestrus more than twice
annually if allowed to breed.
The polecat is also moncestrous, but breeds only once a
year. Mr. Cocks informs me that in captivity the young of
this animal are generally born in the first half of June, and that
the gestation period, as in the ferret, is about forty days.
The stoat, weasel, and pine-marten, in their wild state, are
almost certainly moncestrous and breed once a year. In the
last-mentioned animal Cocks l found that a single oestrus may
last a fortnight. The stoat and weasel do not appear to have
been bred in captivity. The otter in a state of nature breeds
only once a twelvemonth (in winter, as a rule, but young may
be born at any season according to Cocks). In captivity, how-
ever, oestrus may recur at regular monthly intervals all the
year round.2
The various species of seals are in all probability monoestrous,
and have one litter of young annually. Some species show
an almost perfect rhythmic regularity in the recurrence of their
breeding season. Thus, in the case of the harp seal in the north-
east of Newfoundland, and also in Greenland, according to
Millais,3 the pups are born each year between March 8th and 10th.
1 Cocks, " Note on the Gestation of the Pine-Marten," Proc. Zool. Soc., 1900.
2 Cocks, " Note on the Breeding of the Otter," Proc. Zool. Soc., 1881.
Mr. Cocks' subsequent experience concerning which he has been kind enough
to write to me, confirms the conclusion that there is no anoestrous period in
the otter in captivity. There has been some controversy regarding the
breeding of the badger. According to Meale- Waldo the period of gestation
is between four and five months (The Badger: its Period of Gestation,"
Zoologist, 1894), but according to Cocks ( ' The Gestation of the Badger,"
Zoologist, 1903, 1904), this period may be anything between under five and
over fifteen months, for although the sexual season may apparently occur at
any time of the year, the young are invariably born within a period limited
to six weeks. This extraordinary conclusion is based on a number of
observations. Fries (" Uber die Fortpflanzung von Meles taxus" Zool. Anz.,
vol. iii., 1880) describes the badger's ovum as undergoing a resting stage
during which development is at a standstill (cf. roe-deer, p. 47).
3 Millais, loc. cit.
60 THE PHYSIOLOGY OF REPRODUCTION
Farther north, however, at Jan Mayen, they are not born until
about March 23rd or 24th. Turner's notes l on the breeding
habits of seals also point to the conclusion that the sexual
season with these animals is restricted to regular periods of com-
paratively short duration, so that it may probably be assumed
that seals are moncestrous. The males of seals, as already
remarked, experience rut at the time of the female sexual
season. Whether the male generative organs are functional (e.g.
whether the testes produce sperms) at other times does not
appear to be known. It is of interest to note that in many
species the rut is experienced during a period of complete fasting.
Thus it is stated that the male fur seal, after coming to land,
may live for over a hundred days without taking food, and that
during this period he is constantly engaged in struggles with
other males, finally leaving the shore in a state of extreme
emaciation.
The walrus affords an example of a Mammal which bears
young only once in three years. Parturition takes place about
May or June, and the sexual season recurs about two years
subsequently. Thus the nursing or lactation period extends
for nearly two years, while gestation lasts about one year.2
INSECTIVORA
The majority of the animals in this order are almost
certainly polyoestrous, but comparatively little is known con-
cerning their breeding habits. The shrew in this country may
be found breeding in any month from April until November, so
that it is practically certain that this animal is polyoestrous, and
may have two litters, if not three litters in a year. It is ex-
tremely probable also that the water-shrew breeds twice a year.
In the hedgehog in this country, litters are born at the end of
May or June, and in August or September.3 In Germany it is
said that the breeding season extends from March until July.4
1 Turner, "On the Placentation of Seals," Trans. Roy. Soc. Edin., vol.
xxvii., 1875.
2 Millais, loc. cit.
3 Millais, The Mammals of Great Britain and Ireland, vol. i., London,
1904.
4 Van Herwerden, " Beitrag zur Kenntniss des menstruellen Cyklus,"
Monatsschr. f. Geburtshulfe und Gynak., vol. xxiv., 1906.
THE (ESTROUS CYCLE IN THE MAMMALIA 61
The period of gestation in the hedgehog is not more than one
month. The Malayan hedgehogs Gymnum and Hylomys are
stated to experience an uninterrupted poly oestrum.
In the mole a great development of the male generative"
organs begins to take place at the end of January, culminating
at the end of March. Previous to the end of January it is a
matter of great difficulty to distinguish the males from the
females without having recourse to dissection. The testicles lie
on each side of the urinary bladder within the peritoneal cavity.
In March they are protruded into sacs, which look like a con-
tinuation of the peritoneal cavity beneath the base of the tail.
Meanwhile the seminiferous tubules within the testicles undergo
enlargement, and cells are proliferated, which give origin
to the spermatozoa. The prostatic glands, which begin to
increase in size in February, acquire enormous dimensions, and
conceal the urinary bladder at the end of March 1 (cf. hedgehog,
p. 238). At the beginning of the breeding season the male moles
fight one another with great ferocity, and one is often killed.
Pairing takes place at the end of March, or in April, or some-
times as late as early May. A second litter of moles may be
born later in the year, but this fact has not been definitely
proved.2
It would appear that in some Insectivores the prooestrum
may be comparatively severe, for in Tupaia javanica Stratz 3
has described a " menstrual " blood-clot which contained pieces
of desquamated epithelium.
CHIROPTERA
As will be explained more fully in a future chapter,
some species of bats appear to be exceptional in that the
season of oestrus does not synchronise with the period of
1 Owen, loc. cit. The same authority states that in the Cape mole (Chryso-
chloris) he found the testes near the kidneys, but that the vasa deferentia
had a convoluted course, which showed that they underwent periodic
movements. Owen also describes the vesiculse seminales in the hedgehog
as growing to an enormous size at the season of rut.
2 Millais, loc. cit. See also Adams, " A Contribution to our Knowledge of
the Mole," Manchester Lit. and Phil. Soc. Mem., 1902.
3 Stratz, Dcr geschlechtsreife Saiigethiereier stock, Haag, 1898.
62 THE PHYSIOLOGY OF REPRODUCTION
ovulation. It has been shown by Benecke,1 Eimer,2 van
Beneden,3 and Salvi, that whereas copulation may occur in the
autumn, the ova are not fertilised until after the winter
hibernation, the spermatozoa in the meantime lying dormant.
Salvi,4 however, describes the bats in the Grotta dell' Inferno,
near Sassari, as copulating also in the spring, but it is suggested
that coition at this season may only take place among those
females which have failed to become inseminated effectively in
the previous autumn.5 It does not appear to be known whether
the polycestrous condition ever occurs in bats.
It is stated that a " menstrual " (procestrous) flow has been
observed in the flying fox (Pteropus).6
PRIMATES
Lemurs. — Among Lemuroids, Stratz 7 has shown that in
Tarsius spectrum there is a sanguineous prooestrous discharge
almost as concentrated as in monkeys. This is presumably
followed by an cestrous period. It is stated also that Tarsius
experiences an uninterrupted series of dioestrous cycles (i.e. a
condition of continuous polycestrum) ; but that, whereas con-
ception is possible at any time of the year, breeding occurs
more frequently in October and November than at other seasons.8
Monkeys. — The essential similarity between the procestrum in
the lower Mammalia and menstruation in monkeys will be made
clear in the next chapter, when the histological changes which
occur in the uterus are described. The consideration of the sub-
ject, however, is somewhat complicated by the fact pointed out
by Heape 9 that, whereas monkeys may have a continuous series
1 Benecke, " Ueber Reifung und Befruchtung des Eies bei den Fleder-
maiisen." Zool. Anz., vol. ii., 1879.
2 Eimer, "Ueber die Fortpflanzung der Fledermaiise," Zool. Anz., vol. ii.
1879.
3 Van Beneden, " Observations sur la Maturation, la Fecondation, et la
Segmentation de 1'oeuf chez les Cheiropteres, Arch, de Biol., vol. i., 1880.
4 Salvi, " Osservazioni sopra 1'Accoppiamento dei Chirotteri nostrani,"
Atti della Societd Toscana di Scienze Naiurali. vol. xii., 1901.
5 Duval, " Etudes sur 1'Embryologie des Cheiropteres," Premiere Partie,
Paris 1899.
6 Wiltshire, loc. cit. 1 Stratz, loc. cit.
8 Van Herwerden, loc. cit. 9 Heape, loc. cit.
THE (ESTROUS CYCLE IN THE MAMMALIA 63
of dicestrous cycles usually at regular monthly intervals, they are
not necessarily capable of breeding at every heat period. Thus
there is evidence that in the gorilla and chimpanzee in West
Africa there is a special sexual season,1 and Heape 2 has shown
that the same can be said of Semnopithecus entellus and Macacus
rhesus in India, but that the exact time for breeding varies in
the different localities. Thus in Simla Macacus rhesus copulates
about October, and gives birth to young about August or
September in the following year, whereas on the plains around
Muttra it seems probable that March is the usual month when
young are born. However, Mr. Sanyal, the Superintendent of
the Zoological Gardens in Calcutta, expressed the opinion that
M. rhesus can breed at all times of the year. On the other hand,
it has been shown by van Herwerden 3 that Cercocebus in the
Island of Banha breeds only, as a rule, in the late summer or
early autumn.
Heape 4 states that in the Moor macoe in the Gardens in
London there is definite oestrus which always occurs after the
cessation of the menstrual discharge, and persists for two or
three days, and Ellis 5 has shown that this is also probably the
case with the orang utan as well as with various monkeys.
Pocock 6 has given some interesting details concerning the
phenomena which attend the menstrual process in various
monkeys and baboons in the Zoological Society's Gardens. He
states that the females of many species at about the time of
menstruation exhibit extreme inflammation of the naked area
surrounding the genital and anal orifices. An inflammatory
swelling was noticed in various species of Cercocebus, and Papio
and in Macacus nemestrinus,7 but not in Cercopithecus, or in
1 Winwood Reade, Savage Africa, London. Mohrike, Das Ausland,
1872. Garner, Gorillas and Chimpanzees, 1896.
2 Heape, " The Menstruation of Semnopithecus entellus" Phil. Trans. B.t vol.
clxxxv., 1894. "The Menstruation and Ovulation of Macacus rhesus" Phil.
Trans. B., vol. clxxxviii., 1897.
3 Van Herwerden, loc. cit. 4 Heape, " The Sexual Season," &c.
6 Havelock Ellis, Psychology of Sex, vol. ii., Philadelphia, 1900.
6 Pocock, " Notes upon Menstruation, Gestation, and Parturition of some
Monkeys that have lived in the Society's Gardens," Proc. Zool. Soc., 1906.
7 Similar observations had been previously described in Cercopithecus,
Papio, and other species by certain of the older naturalists. See St. Hilaire
and Cuvier, Hist. Nat. des Mammiferes, 1819-35.
64 THE PHYSIOLOGY OF REPRODUCTION
certain other species of Macacus including M. rhesus. Heape,
however, states that in menstruating specimens of M . rhesus
observed by him, and M. cynomolgus, the skin of the buttocks
became swollen and red or purple in colour, as well as the skin
of the abdomen, the inside of the thighs, and the under surface
of the tail, while the skin of the face tended to become flushed
or blotched with red ; at the same time the nipples and vulva
were congested. Menstrual haemorrhage has been recorded in
many monkeys and baboons, but there appears to be consider-
able variability in its extent. Pocock says : "In baboons it
may or may not take place, and may be great or little in amount.
It has been noticed to occur in some profusion in a female of
Macacus sinicus, and not to occur appreciably in a female of
the closely allied species, M. fascicularis. Obviously, therefore,
it cannot be associated with the inflammatory swelling of the
genito-anal region [since no swelling was apparent in either of
these two species] ; and it is hardly likely to have a specific
value in taxonomy. Perhaps the nearest guess that can at
present be made is the surmise that it is dependent on the con-
stitution or health of the individual."
Heape noticed that in M. rhesus the menstrual discharge
lasted for from three to five days. Pocock records that in a
Chacma baboon (Papio porcarius) haemorrhage continued for
about four days. In both animals the phenomenon was truly
" menstrual " (i.e. of monthly occurrence).
Pocock records the interesting fact that whereas the swelling
of the inflammatory area commences at about the same time
as the haemorrhage, it does not reach its full size until several
days after the discharge is over. It soon afterwards begins to
shrink, and in about another two weeks has disappeared, so that
the female at a distance is indistinguishable from the male. After
a few days' rest inflammation again sets in, and the process is
repeated. Pocock suggests that this sub-caudal swelling may
serve the purpose of apprising the male (at a distance) as to
when the female is " on heat," and it is to be noted that it is at
its maximum after menstruation is over (as just mentioned),
and so presumably therefore during a definite period of
oestrus.
The question as to the correspondence in time between the
THE (ESTROUS CYCLE IN THE MAMMALIA 65
processes of menstruation and ovulation is discussed in a later
chapter.
Little is definitely known concerning the length of the
gestation period in the various apes and monkeys. Pocock's
observations show that in Macacus nemestrinus this period is
between six and seven months. Blandford l states his belief that
about seven months is the usual period for the genus Macacus.
Sanyal, according to information recorded by Sclater,2 found
that a female of Cercopithecus cynosurus in the Zoological
Gardens, Calcutta, carried her young for seven months.
Gestation in the Quadrumana is dealt with at some length
by Breschet,3 who cites many of the older observations. He
shows that the question as to the duration of the period is com-
plicated by the fact that monkeys, unlike the majority of
Mammals, may copulate at other times than the breeding
season, and that they are said occasionally to experience men-
struation during pregnancy.
Man. — As is well known, menstruation recurs normally in the
non-pregnant human female at intervals of from twenty-eight to
thirty days. The exceptions to this general rule are, however,
very numerous, and have often been noticed. Thus the interval
may be extended to five weeks, or be abbreviated to two weeks
without any derangement to the general health. " In one
hundred women, sixty-one [were found] to menstruate every
month, twenty-eight every three weeks, ten at uncertain in-
tervals, and one, a healthy woman aged twenty-three years,
every fortnight/' 4 The duration and amount of the discharge
may also vary considerably both in different women and in
the same woman at different times.
It is stated, also, that the periodicity of menstruation depends
partly on the climatic conditions, and that women in Lapland
1 Blandford, The Fauna of British India, vol. i., London, 1888.
2 Sclater, Mammals of South Africa, London.
3 Breschet, " Recherches anatomiques et physiologiques sur la Gestation
des Quadrumanes," Memoires de I'Acad. des Sciences, vol. xix. , 1845.
4 Laycock, loc. cit., and Havelock Ellis, loc. cit. There is in some cases a
tendency for the cycle to become divided up into two cycles, separated by
the so-called " Mittelschmerz," or inter- menstrual pain, which is occasion-
ally accompanied by a sanguineous discharge. (Halliday Croom, "Mittel-
schmerz," Trans. Edin. Obstet. Soc., vol. xxi., 1896).
E
66 THE PHYSIOLOGY OF REPRODUCTION
and Greenland menstruate less frequently, whereas in certain
low and hot countries the catamenia may recur every three
weeks.1
Further, the regularity with which the menstrual periods
occur is liable to be disturbed by environmental changes. Thus,
it is stated that change of residence, or foreign travel, without
otherwise affecting the health, may bring about amenorrhcea or
a temporary cessation of menstruation.2 Such an effect is, no
doubt, comparable to the well-known influence of captivity or
change of environment in arresting the sexual functions of
many animals.
The commonest time for the continuance of the menstrual
flow is said to be about three or four days in this country, but
it may last for as long as eight days, or, on the other hand, for
only a few hours without disturbance of health. It usually
begins gradually, becoming most profuse about the second or
third day, and then diminishes.3 The total amount of blood
lost has been variously estimated at from two to four ounces.
In hot climates the quantity is greater than in cold ; and it is
said to be increased by luxurious living, and also by abnormal
mental stimulation. The character of the menstrual discharge
and its source of origin can best be considered in describing the
histology of the uterus during the oestrous and menstrual cycles
(see Chapter III.).
The monthly development of the uterine mucous membrane
which precedes the menstrual discharge is often accompanied
by a fulness of the breasts which begins to disappear after the
commencement of the flow. Swelling of the thyroid and
parotid glands, and tonsils, as well as congestion of the skin
and a tendency towards the formation of pigment, are also
1 Matthews Duncan, "Sterility in Women," Brit. Med. Jour., 1883 ; and
Laycock, loc. cit.
2 Wiltshire, loc. cit.
3 Galabin, A Manual of Midwifery, 6th Edition, London, 1904. The age
at which menstruation begins varies in different countries, being earlier in
warm climates than in cold ones. In our own country the first menstrua-
tion does not usually occur before the age of fourteen or fifteen, while the
menopause (or period when menstruation ceases) begins about the age of
forty-five. (See p. 672.) Kennedy (Edin. Med. Jour., vol. xxvii., 1882), how-
ever, has reported a case of a woman who continued to menstruate after
giving birth to a child at the age of sixty-three.
THE (ESTROUS CYCLE IN THE MAMMALIA 67
known to occur.1 The voice also is liable to be affected at the
menstrual periods, and the skin and breath sometimes have a
peculiar odour. Mental depression may exist, and be accom-
panied by nervous pathological phenomena.
According to the upholders of the " Wellenbewegung "
hypothesis 2 the reproductive life of the human female consists
of a succession of wave-like periods which follow the monthly
cycle. Thus, according to Stevenson,3 the curve of temperature
FIG 1. — Diagram illustrating the "Wellenbewegung" hypothesis. The
curve AB represents the varying intensity of the vital processes during
the twenty-eight days of the menstrual cycle. The numbers between
m and n represent the days occupied by menstruation. (From Sellheim.)
is above the mean line for about half the month, when it rises
to half a degree above the mean. It falls below the mean line
just before the onset of menstruation, during which it remains
about half a degree below. Similar results were obtained by
1 See p. 350, Chapter IX.
2 Godman, "The Cyclical Theory of Menstruation," Amer. Jour. Obstet.,
vol. xi , 1878. Reinl, " Die Wellenbewegung des Lebensprozesses des Weibes,"
Volkmann's Sammlung klin. Vortrage, No. 273. Ott, " Les lois de la periodicity
de la fonction physiologique dans 1'organisme feminine," Nouvelles Arch,
d' Obstet. et de Gijnec., 1890.
3 Stevenson, "On the Menstrual Wave," Amer. Jour. Obstet., vol. xv., 1882.
68 THE PHYSIOLOGY OF REPRODUCTION
Reinl, Ott, and Giles,1 but Vicarelli 2 and certain other authors
have recorded an increased temperature during menstruation.3
Zuntz,4 however, as a result of more recent experiments, says
that there is a regular lowering of the temperature throughout
the menstrual period, after which it rises to the normal.
Stevenson states also that the curve of urea excretion follows
a similar course to the temperature curve, and that, speaking
generally, there is an increase in metabolism coincident with the
time of development of the uterine mucosa. There is, however,
no doubt much truth in von Noorden's criticism 5 that the
" menstrual wave " hypothesis has given occasion to many pre-
mature conclusions regarding the behaviour of the metabolism.
Schroder,6 who investigated the nitrogen metabolism, found a
retention of nitrogen immediately before and during menstrua-
tion (cf., Potthast, &c., for dogs, p. 54), but other investigators
have obtained somewhat different results.7 Zuntz has shown
from numerous experiments that, contrary to the conclusions of
other authors, there is no evidence of a constant variation in
the respiratory exchange during the menstrual cycle.
Mosher 8 states that there is a fall of blood pressure at the time
of menstruation. Zuntz 9 records a diminution in the pulse rate.
Sfameni 10 states that there is a decrease in the quantity of
haemoglobin in the blood during menstruation. He says also
that the number of blood corpuscles increases in the days imme-
diately preceding the haemorrhage, but is diminished during it.11
1 Giles, " The Cyclical or Wave Theory," &c., Trans. Obstet. 8oc., London,
vol. xxxix., 1897.
2 Vicarelli, "La temperature de I'ute'rus dans ses diverses conditions
physiologiques," Arch. Ital. de Biol., vol. xxxii., 1899.
3 Sfameni, "• Influence de la menstruation sur la quantite d'hemoglobine,"
Arch. Ital. de Biol., vol. xxxii., 1899.
4 Zuntz (L.), " Einfluss der Ovarien auf den Stoffwechsel," Arch.f. Gynak.,
vol. Ixxviii., 1906.
5 Von Noorden, Metabolism and Practical Medicine (English Translation),
vol. i., London, 1907.
6 Schroder, '- Untersuchungen liber den Stoffwechsel wahrend der Men-
struation," Zeitsclir.f. klin. Medicin, vol. xxv. , 1894.
7 See von Noorden. loc. cit.
8 Mosher, " Blood -pressure during Menstruation," Johns Hopkins Hospital
Bulletin, 1901. 9 Zuntz, loc. cit. 10 Sfameni, loc. cit.
11 Cf. Carnot and De8andre, " Variations du nombre des Hematics chez la
Femme pendant la pe'riode menstruelle," C. R. de la Soc. de Biol , vol. Ixvi.,
1909.
THE (ESTROUS CYCLE IN THE MAMMALIA 69
Birnbaum and Osten l state that in the blood of menstruating
women coagulation is retarded. This statement is based on
experiments made by adding fibrinogen to menstrual blood
serum.
Blair Bell 2 states that in connection with menstruation
there is a marked drop in the calcium content of the systemic
blood, and that this is most marked just before bleeding begins.
This is correlated with an excretion of calcium salts in the
menstrual discharge, an examination of which revealed the
presence of a considerable quantity of calcium, both free and
within the leucocytes (see p. 87). This excretion of calcium
during menstruation is regarded by Blair Bell as connected
phylogenetically with the process of egg-formation by birds and
other lower Vertebrates.
According to Martin,3 and certain other writers, the human
female often experiences a distinct post-menstrual oestrus, at
which sexual desire is greater than at other times ; so that,
although conception can occur throughout the inter-menstrual
periods, it would seem probable that originally coition was
restricted to definite periods of oestrus following menstrual or
prooestrous periods in women as in the females of other
Mammalia. On this point Heape writes as follows :— ' This
special time for oestrus in the human female has very fre-
quently been denied, and, no doubt, modern civilisation and
modern social life do much to check the natural sexual instinct
where there is undue strain on the constitution, or to stimulate
it at other times where extreme vigour is the result. For
these reasons a definite period of oestrus may readily be
interfered with, but the instinct is, I am convinced, still
marked/' 4
Heape has also given a brief resume* of the evidence that
primitive Man resembled the lower Primates in having a definite
sexual season. The evidence is based largely upon the works of
1 Birnbaum and Osten, " Untersuchungen iiber die Gerinnung des
Blutes wiihrend der Menstruation," Arch. f. Gyndk., vol. Ixxx., 1906.
- Blair Bell, " Menstruation and its Eelation to the Calcium Metabolism."
Proc. Roy. Soc. Med., July 1908.
3 Martin, "The Physiology and Histology of Ovulation, Menstruation,
and Fertilisation," Hirst's System of Obstetrics, vol. i., London, 1888.
4 Heape, loc. cit.
70 THE PHYSIOLOGY OF REPRODUCTION
Ploss 1 and Westermarck,2 the latter of whom goes somewhat
fully into the subject in a chapter on " A Human Pairing Season
in Primitive Times/' to which the reader is referred for further
references on this subject.3
It has been shown that there is a more or less restricted
season for breeding among certain of the North American
Indians, among certain tribes in Hindustan, among many of the
native Australians, among the Esquimaux, among the natives of
the Andaman Islands, as well as among certain other of the more
primitive races of mankind. The season seems generally to
occur in the spring, but this is not invariably so. Annandale
and Robinson 4 state that among the Semang or aboriginal
tribes of the Siamese State of Jalor, children are generally
born only in March, or immediately after the wet season, a fact
which appears to imply that there is a regular sexual season
in June.
Further evidence of the existence of a primitive sexual
season in Man is furnished by the records of the annual feasts
which the ancients indulged in — usually in the spring — and
which Frazer 5 has shown to be represented in modern European
countries by the May-queen festivals, and other similar customs
that have survived into our own time. It is well known that
the ancient festivals among the civilised peoples of the past
were times of great sexual licence, and so in all probability
were similar in origin to the licentious feasts and dances of
various savage races at the present day. Their anthropological
significance and the intimate association between them and
the idea of reproduction are discussed at great length by Frazer
in his book entitled The Golden Bough.
There is, moreover, evidence of a human pairing season in
the higher birth-rate which occurs at certain seasons in various
countries at the present day. Ploss has collected statistics
illustrating this fact in Russia, France, Italy, and Germany,
1 Ploss, Das Weib, Leipzig, 1895.
2 Westermarck, The History of Human Marriage, London, 1891.
3 See also Havelock Ellis, loc. cit.
4 Annandale and Robinson, Fasciculi Malayenses : Anthropology, Part I.,
1903.
5 Frazer, The'jGolden Bough, 2nd Edition, London, 1900.
THE (ESTROUS CYCLE IN THE MAMMALIA 71
and Haycraft 1 has shown that there are indications of a similar
condition existing in Scotland. On this subject Mayo-Smith 2
writes as follows : " The largest number [of births] almost
always falls in the month of February . . . corresponding to con-
ceptions in May and June. . . . Observations tend to show the
largest number of conceptions in Sweden falling in June ; in
Holland and France, in May-June ; in Spain, Austria, and
Italy, in May ; in Greece, in April. That is, the farther south,
the earlier the spring and the earlier the conceptions/' Other
facts of a like kind are recorded by Westermarck, who concludes
that primitive Man had an innate tendency towards increased
powers of reproduction at the end of spring or beginning of
summer, and that this tendency became variously modified
under the influence of natural selection in the different human
races which subsequently arose.3
Finally, it may be pointed out that Westermarck's conclusion
— which seems a very probable one in view of the evidence
which he and others have collected — is in no way invalidated
by the fact that the human female experiences normally an
uninterrupted succession of dioestrous (i.e. menstrual) cycles ;
for, as already shown, a similar condition is known to exist in
several at least of the lower Primates, with which there is also
evidence that in a state of nature the breeding functions are
restricted to particular seasons of the year.4
1 Haycraft, "On some Physiological Kesults of Temperature Variations,"
Trans. Roy. Soc. Edin., vol. xxix., 1880.
2 Ma3ro-Smith, Statistics and Sociology, vol. i., New York, 1895. Cf. also
van Herwerden, loc. cit.
3 Mayo-Smith (loc. cit.) points out that sexual periodicity in civilised Man is
much obscured by social influences. " One great social influence is the time
of marriage. Marriage tends to accumulate about the social festivities of
Christmas time, and in Catholic countries especially in the period just before
Lent." He suggests that in agricultural districts the concentration about
Christmas is due to the leisure following the labours of the autumn. " In
cities the births are more evenly distributed, showing that artificial life has
overcome the influence of seasons and particular occupations."
4 That is to say that, whereas menstruation goes on at regular intervals all
the year round, the prooestrous or menstrual periods are only followed during
the breeding season by cestri at which it is possible for conception to occur.
There are some indications that the sexual instinct among males is also
periodic, both in the lower Primates and in the human subject, but the
periodicity is not so marked as among females. Havelock Ellis (loc. cit.) has
72 THE PHYSIOLOGY OF REPRODUCTION
Whether the moncestrous or the polycestrous condition is the
more primitive is a question which cannot at present be decided.
The fact that polycestrum is secondarily acquired among many
animals may perhaps be regarded as evidence that moncestrum is
the more primitive of the two conditions ; for, as already shown,
there are numerous instances of Mammals which are almost
certainly moncestrous in their wild state, but which have inde-
pendently assumed a condition of polyoestrum under the more
luxurious influences of domestication. Thus, while the sheep,
the sow, and the cat are almost certainly monosstrous in a
state of nature, the domesticated breeds of these animals show
a varying degree of polyoestrum which appears to depend
largely upon the extent to which domestication has been carried
as well as upon food and the influences of the surroundings.
On the other hand, the existence of the continuous polycestrum
in tropical climates among such primitive Mammals as the
Insectivores, and the common occurrence of varying degrees of
polyoestrum among the Rodents, not only in captivity but also
in the wild state, point to the possibility that polyoestrum may
in reality be the more primitive condition, and one which can
easily be reverted to under the influence of a favourable en-
vironment.
The main purpose of polyoestrum (to use teleological lan-
guage) is no doubt, as already remarked, to provide increased
opportunity for coition, and so to promote the fecundity of the
race. But it must be remembered that oestrus is not necessarily
associated with ovulation, and consequently the explanation
just given of the polycestrous habit is not of universal application.
This is a point which will be referred to again in dealing with
ovulation. It is of course possible, however, that the poly-
cestrous condition, having once been acquired, might in certain
circumstances be perpetuated in spite of its inutility.
Before concluding the present chapter it remains for me to
allude briefly to the effect of maternal influences on the oestrous
cycle. These, as pointed out by Heape, may or may not corn-
discussed this question at some length, adducing evidence of a sexual rhythm
in men. See especially appendix to Ellis's work by Perry-Coste, who shows
that there may be a tendency towards rhythmic regularity in the sexual
functions as manifested especially in the recurrence of seminal emissions.
THE (ESTROUS CYCLE IN THE MAMMALIA 73
pletely disorganise the recurrence of the sexual season. In such
animals as the dog they do not do so, because the dog is mon-
cestrous, and has, as a rule, only two sexual seasons annually,
so that the anoestrous period considerably exceeds in length
the period of gestation. In large animals such as the camel,
on the other hand, where the gestation period extends for
thirteen months, the recurrence of the sexual season is post-
poned by pregnancy for a whole year. Again, in small animals
like the rat, gestation only prevents the recurrence of oestrus,
reducing the number of dicestrous cycles, but not interfering
with the recurrence of the sexual season. " But whenever
gestation occurs it encroaches upon, if it does not entirely
absorb, the ancestrum ; that is to say, it reduces the -period
during which the generative organs would lie fallow if the sexual
season were a barren one. Thus in the case of a mare, a barren
sexual season may consist of a series of dioestrous cycles lasting
for as long as six months, in which case the anoestrum lasts
six months also, after which another sexual season begins. A
reproductive sexual season, however, results in a period of
eleven months' gestation, interfering not only with the di-
cestrous cycles which would have recurred if conception had
not taken place, but also absorbing practically the whole of the
anoestrum/' 1
The duration of the gestation period is intimately connected
not only with the size of the body, but also with the stage of
development at which the young are born.2 It is longest in the
large terrestrial and gigantic aquatic Mammals (Ungulata and
Cetacea), which live amid favourable conditions of nourishment.
With these animals the young are so far advanced in develop-
ment at the time of birth that they are able to follow the mother
about, and to a certain extent shift for themselves. In Carnivores
and Rodents the period of pregnancy is relatively shorter, and the
young are often born naked, and with unopened eyes, and con-
sequently are absolutely helpless for a considerable time after
birth. The gestation period is shortest in the aplacental
Mammals (Monotremata and Marsupialia), in which the young
are born at a very early stage and transferred to a pouch
1 Heape, loc. cit.
2 Sedgwick, Student's Text-book of Zoology, vol. ii., London, 1905.
74 THE PHYSIOLOGY OF REPRODUCTION
formed by cutaneous folds in the vaginal region. In Mono-
tremes the young are hatched from eggs which, after being laid,
are deposited in the pouch.
The question as to what are the precise factors which de-
termine the length of the gestation period has already been
referred to in the first chapter, where it was pointed out that both
the duration of pregnancy and the time of the year at which
breeding occurs are necessarily controlled by natural selection,
acting in the interests of the next generation.
The effects of lactation upon the recurrence of oestrus vary
widely, and are often different among individuals belonging to
the same species. Thus, although the mare as a general rule
is capable of becoming pregnant while suckling, in some
individuals the sexual season is postponed, the mares only
becoming pregnant once in two years.
The return of menstruation during lactation in women has
been dealt with recently by Heil,1 and Ding wall Fordyce.2
Heil, who had studied the conditions of two hundred nursing
mothers, expresses the belief that the occurrence of menstruation
and not the condition of amenorrhcea is the normal state
during lactation, but that menstruation is not so frequent in the
later lactations as during the earlier ones. Fordyce has reached
similar conclusions, finding that menstruation occurred during
lactation in forty per cent, of the cases in which suckling was
performed, while in ninety-two per cent, of the cases its return
was within nine months of parturition, and that menstrua-
tion during lactation was commoner with the earlier than with
the later lactations, showing that age is an important factor.
The histological changes which occur in the internal gene-
rative organs of various Mammalia during the cestrous cycle
are described at some length in the succeeding chapters.
1 Heil, " Laktation und Menstruation/' Monatsschr.f. Geburtsh. u. Gynak.,
vol. xxiv., 1906.
2 Fordyce, "An Investigation into the Complications and Disabilities of
prolonged Lactation." Being an extension of papers published in The Lancet,
Part I., 1906, The Brit. Med. Jour., Part I., 1906, and The Brit. Jour, of
Children's Diseases, 1906. Gellhorn ("Abnormal Mammary Secretion,"
Jour. Amer. Mcd. Assoc., Nov. 21, 1908) mentions a case of an ape
(Cercopithecus) in which menstruation always disappeared during profuse
lactation, but reappeared as soon as the mammary secretion ceased or became
markedly decreased.
CHAPTER III
THE CHANGES THAT OCCUR IN THE NON-PREGNANT
UTERUS DURING THE (ESTROUS CYCLE
" Menstruation is like the red flag outside an auction sale ; it shows that
something is going on inside." — MATTHEWS DUNCAN.
FOR full descriptions of the morphology of the uterus in the
different mammalian orders, reference may be made to the
text-books on human, comparative, and veterinary anatomy.
But before passing on to describe the changes which occur in
the histology of the uterus during the menstrual cycle, it may
not be out of place to remind the reader of the general structural
relations of the generative organs in the human female.
The two ovaries, the structure of which is described in the next
chapter, are situated one on each side of the pelvis, and are
connected with the posterior layer of the broad ligament of
the uterus. In connection with each ovary is a Fallopian
tube or oviduct, which opens into the peritoneal cavity about
an inch from the ovary.1 Surrounding the orifice is a fringe
of irregular processes or fimbrise, which, when expanded, assist
in directing the ovum in its passage into the tube. The tubes
are about four inches long, and terminate at the superior angles
of the uterus, with the cavity of which they are in continuation.
They are surrounded by an external serous coat derived from
the peritoneum, a muscular coat containing both longitudinal
and circular fibres, and an internal mucous membrane, which
is highly vascular and is lined within by a ciliated epithelium.
1 A vestigial structure lying transversely between the ovary and the
Fallopian tube on either side is called the parovarium or epoophoron, or
organ of Rosenmiiller, or sometimes the duct of Gartner. It consists of a
few scattered tubules, with no aperture. It is the homologue of the epi-
didymis of the male. Vestiges of structure corresponding to the organ of
Giraldes are also sometimes found in the vicinity of the parovarium, but
nearer to the uterus. These have been called the paroophoron.
75
76 THE PHYSIOLOGY OF REPRODUCTION .
The human uterus consists of two parts, the corpus or body
of the uterus, and the cervix or neck, which opens into the vagina.
The body of the uterus contains the following layers, which
correspond with those of the Fallopian tubes : (1) A serous
layer ; (2) a thick muscular layer, consisting of three more or
less blended sub-layers ; and (3) a still thicker layer, known as
the mucous membrane or mucosa (sometimes called the endo-
FIG. 2. — Transverse section through Fallopian tube, showing folded
epithelium and muscular coat.
metrium), which is composed of a connective tissue containing
spindle-shaped cells, and is lined by a ciliated epithelium
bounding the uterine cavity. The mucosa contains numerous
tubular glands, which open out into the cavity of the uterus
and are covered by an epithelial layer, these being continuous
with the epithelium of the surface. The sub-epithelial mucosa,
which is sometimes called the uterine stroma, contains also a
number of blood-vessels and lymph spaces. The vessels are
branches of the ovarian and uterine arteries and veins. The
CHANGES IN THE NON-PREGNANT UTERUS 77
uterus is also supplied by nerves which are referred to in a
future chapter (p. 527).
In many of the lower Mammals the uterus is represented by
two tubes, called the horns of the uterus or uterine cornua,~
which may unite posteriorly to form the corpus, or may, on the
other hand, open separately into the vagina. The arrangement
FiG. 3. — Section of a cornu of a rabbit's uterus.
s, Serous layer ; Im, longitudinal muscle fibres ; cm, circular muscle fibres ;
a, areolar tissue with large blood-vessels ; mm, muscularis mucosae ; m,
mucosa. (From Schafer.)
of the different layers in each of the cornua is essentially similar
to that presented by the corpus uteri in the human species.
The neck or cervix uteri, which is narrower than the rest of
the organ, opens into the vagina by a transverse aperture
known as the os. The vagina is the broad passage from the
uterus to the exterior. Its walls contain both longitudinally
and circularly arranged muscle fibres. Internally it is lined
78 THE PHYSIOLOGY OF REPRODUCTION
by a stratified scaly epithelium, surrounded by erectile tissue.
The entrance to the vagina from the exterior is guarded by a
thin fold of mucous membrane, which usually becomes per-
forated at the first coition. This structure, which is called the
hymen, is peculiar to the human race.1
The vulva comprises the female generative organs which
are visible externally. These include the mons veneris, the
FIG. 4. — Cross-section through cervical canal of human uterus. (From
Williams' Obstetrics. Appleton & Co.)
labia majora and minora, and the clitoris. The last-mentioned
structure is a small erectile organ, which is homologous with the
penis.2
THE CYCLE IN MAN
In giving an account of the changes which take place
in the uterus during the menstrual cycle of the human female,
it will be convenient to adopt the scheme of classification
employed by Milnes Marshall 3 in his work on Vertebrate
1 The significance or function of the hymen is not certainly known.
Metchnikoff (The Nature of Man, English Edition, London, 1903) suggests
that it may have been useful in the earlier history of the race, when sexual
intercourse probably occurred at an early age, before the reproductive organs
were mature. Under such circumstances the hymen, instead of being a
barrier, may have facilitated successful coitus. Metchnikoff supposes the
aperture to have become gradually dilated by repeated intercourse without
being torn, until it admitted of the entrance of the adult male organ.
2 The outer part of the vagina into which the female urethra opens is
often called the vestibule or urogenital sinus.
3 Milnes Marshall, Vertebrate Embryology, London, 1893.
CHANGES IN THE NON-PREGNANT UTERUS 79
Embryology. This classification, as will be seen later, is iden-
tical with that adopted by Heape x in describing the menstrual
-V,.:
FIG. 5. — Section through wall of vagina (upper part) of monkey.
a, epithelium ; &, sub-mucous layer; c, lymphatic gland; d, nerve;
e, Pacinian body ; /, fat cells.
1 Heape, "The Menstruation of Semnopithecus," &c., Phil. Trans., B.,
vol. clxxxv., 1894, and vol. clxxxviii., 1897. A similar classification has been
adopted by Minot (Human Embryology, 1892), who divides the menstrual
process into (1) Tumefaction ; (2) Menstruation ; and (3) Restoration of the
mucosa.
80 THE PHYSIOLOGY OF REPRODUCTION
changes of monkeys. The cycle is divided into four stages,
as follows :—
*
(1) The Constructive Stage.
(2) The Destructive Stage.
(3) The Stage of Repair.
(4) The Stage of Quiescence.
The last stage may conveniently be considered first.
The Stage of Quiescence. — The normal condition of the human
endometrium has been described by Webster,1 to whose account
the reader is referred. This author calls special attention to
the following points : (1) The thickness of the mucosa is not
uniform, but varies considerably. (2) The epithelial cells which
line the mucosa, and also those which line the glands, show
differences in shape and size, and in the position of the nuclei.
(3) The epithelial cells lining the glands are, as a rule, larger
than the superficial cells. (4) The interglandular connective
tissue or stroma is mainly embryonic in nature, and consists of
a nucleated protoplasmic reticulum, containing every stage of
transformation into the more differentiated spindle-shaped cells.
(5) The stroma nearest the surface is for the most part arranged
parallel to it, the cells immediately below the epithelium
forming a kind of basement-membrane. (6) The superficial
portion of the mucosa is supplied only by capillaries. (7) The
line of junction of mucosa and muscle-wall is irregular, and
there is no special muscularis mucosae.
The Constructive Stage. — During this stage the stroma of the
uterus undergoes a process of growth. This is brought about
partly by cell division, partly (according to Engelmann 2) by
an increase in intercellular substance, and partly by an enlarge-
ment of the glands and blood-vessels. According to Lipes,3
this stage commences as soon as the process of regeneration
(following the preceding menstrual period) is completed, which
is about eighteen days after the cessation of the previous
flow. " During the stage of regeneration the cells of the stroma
1 Webster, Human Placentation, Chicago, 1901.
2 Engelmann, " The Mucous Membrane of the Uterus," &c., Amer. Jour.
Obstet., vol. viii., 1875.
3 Lipes, " A Study of the Changes occurring in the Endometrium during
the Menstrual Cycle," Albany Medical Annals, vol. xxv. 1904.
CHANGES IN THE NON-PREGNANT UTERUS SI
lay over each other rather thickly, but now become pressed
apart, particularly in the outer third of the mucosa. The
protoplasm of these cells becomes compressed, and the pro-
d
-d'
FlG. 6. — Section through wall of vagina (lower part) of monkey.
«, epithelium lining cavity; b, sub-mucous layer; c, muscular layer;
d, d', nerve ganglia ; e, artery ; /, fat cells.
jections by which they are bound together are either greatly
lengthened or completely separated." The capillaries of the
mucous membrane become congested (Fig. 7), and a serous or
82 THE PHYSIOLOGY OF REPRODUCTION
sanguineo-serous exudate infiltrates into the stroma. The
enlargement of the vessels continues, but does not become very
pronounced until shortly before the stage of destruction which
may be said to mark the beginning of menstruation proper.
Lipes also describes an increase in the size of the glands of
the mucous membrane, which he supposes to be due to the
collection of the secretion of the gland-cells. This mucus-like
FIG. 7. — Section through mucosa of human uterus showing pre-menstrual
congestion. (From Sellheim.)
product of the gland-cells is said to give them a distinctly
granular appearance. " The gland-cells become uniformly
swollen and take stains more evenly, and their nuclei are more
widely separated as a result of the increase in the volume of the
protoplasm, and are uniformly more round in comparison with
the oval nuclei, which are seen in the regeneration period."
Westphalen 1 has pointed out that the nuclei, which are situated
near the base of the cell as a rule, appear in the middle of the
cell at the beginning of the stage of pre-menstrual swelling.
1 Westphalen, " Zur Physiologic des Menstruation," Arch. f. Gyniik., vol.
lii., 1896.
CHANGES IN THE NON-PREGNANT UTERUS 83
As a consequence of these changes the mucosa becomes con-
siderably increased in thickness. Thus, if a woman who had
been menstruating regularly dies shortly before the expected
approach of a menstrual period, the thickness of the mucous
membrane is often as much as one-sixth of an inch at its thickest
part, as compared with a thickness of from one-tenth to one-
twentieth of an inch in women who died within ten days
after the cessation of the flow.1 Leopold 2 has described a
growth so considerable that the uterine cavity, prior to the stage
of bleeding, becomes almost completely obliterated.
It should be mentioned, however, that according to some
authors the amount of pre-menstrual growth in the uterine
mucosa is very slight, while Oliver 3 seems to be doubtful whether
any growth occurs at all, stating that he has made an examina-
tion of uteri at various pre-menstrual and menstrual stages,
and has failed to find any evidence of changes in the mucosa
tissue apart from those directly associated with the phenomena
of bleeding. Westphalen's view appears to be similar ; for,
according to this observer, there is no multiplication of nuclei
during this stage, the pre-menstrual swelling being brought
about entirely by the serous saturation of the stroma.
The Destructive Stage. — At the close of the constructive
period the blood leaves the capillaries and becomes extra-
vasated freely in the stroma, but there has been some dispute
as to how this process is effected. It has been suggested that
the blood transudes through the walls of unruptured capillaries
under the influence of congestion, or that permanent openings
exist from the vessels into the uterine glands, these being closed
normally by muscular contraction ; 4 but the belief now generally
held is that, whereas the walls of many of the congested vessels
break down under pressure, and so freely admit of the exit
of the blood corpuscles into the mucosa tissue, haemorrhage also
takes place partly by diapedesis. Engelmann,5 Williams,6 and
1 Galabin, A Manual of Midwifery, Gth Edition, London, 1904.
2 Leopold, " Untersuchungen Uber Menstruation und Ovulation," Arch,
f. Gyniik., vol. xxi., 1883.
3 Oliver, "Menstruation: its Nerve Origin," Jour. AnaL atul Phys.. vol.
xxi., 1887. 4 Galabin, loc. cit. 5 Engelmann, loc. cit.
6 Williams (Sir J.), " The Mucous Membrane of the Body of the Uterus,"
Obstet. Jour. Gt. Britain vols. iii. and v., 1875 1877.
84 THE PHYSIOLOGY OF REPRODUCTION
others have ascribed the breaking down of the vessel-walls to
fatty degeneration, but this has been denied by Moricke,1 and
more recently by Findley,2 while Leopold has described the
appearance of the fatty degeneration as a result rather than a
cause of haemorrhage.
After the extravasation of blood, the corpuscles tend
to become aggregated in lacunae which lie beneath the superficial
FIG. 8. — Section through mucosa of human uterus showing extravasation
of blood. (From Sellheim.)
epithelium. These lacunae are the sub-epithelial hsematomata of
Gebhard,3 according to whom the epithelium becomes lifted
almost bodily from its bed, the space between it and the stroma
being filled with blood. Gebhard concludes that the blood
eventually reaches the uterine cavity by being forced between
1 Moricke, " Die Uterusschleimhaut in der verschiedenen Altersperioden
und zur Zeit der Menstruation,'-' Zeitsch.f. Geburtshillfe u. Gyndk., vol. vii., 1882.
2 Findley, "Anatomy of the Menstruating Uterus," Anier. Jour. Obstet.,
vol. xlv., 1902.
3 Gebhard, " Ueber das Verhalten der Uterusschleimhaut bei der Men-
struation," Verhand cl. Gesells. f. Geb. u. Gyn. zu Berlin, Zeitsch.f. Geb. u. Gyn.>
vol. xxxii., 1895.
CHANGES IN THE NON-PREGNANT UTERUS 85
the epithelial cells, or that a larger exit is provided by certain
of the cells being carried bodily away. Gebhard also believes
that bleeding may take place into the lumina of the glands.
Christ 1 states that when the menstrual flow is very profuse
there is a considerable loss of surface epithelium, but that in
other cases the removal of epithelium is slight. This author
has also described bleeding into the glands. (Fig. 9.)
Very contradictory statements have been made regarding
the extent to which denudation takes place during menstruation.
Williams (Sir J.), von Kahlden,2 and others among the older
writers, expressed the belief that a large part, if not the whole, of
the uterine mucous membrane was destroyed. This view, as
will be seen later, has been partially confirmed for monkeys by
Heape. It has been pointed out, however, by Whitridge
Williams,3 that the older writers made their observations upon
uteri which had undergone post-mortem changes. The pre-
ponderance of recent opinion appears to be that destruction of
the mucous membrane is, as a rule, confined to the epithelium,
and that this is only partially removed. Among those
who have accumulated evidence in support of this conclusion
are Gebhard, Strassmann,4 Westphalen, Findley, Whitridge
Williams, and Lipes. De Sinety,5 Moricke, and Oliver appear
to uphold the opinion that even the superficial epithelium
remains practically intact. Mandl,6 Maerdervort,7 and also
Champneys 8 have made the exceedingly likely suggestion that
the extent to which the mucosa is destroyed varies within wide
limits in different individuals or even in the same individuals
at different periods of life.
1 Christ, " Das Verhalten der Uterusschleimhaut wahrend der Menstrua-
tion/' Inorg. Dissert., Giessen, 1892.
2 Von Kahlden, " Ueber das Verhalten der Uterusschleimhaut wahrend
und nach der Menstruation," Hegar's Festschrift, Stuttgart, 1889.
3 Whitridge Williams, Obstetrics, London and New York, 1904.
4 Strassmann, "Beitriige zur Lehre von der Ovulation, Menstruation, und
Conception," Arch. f. Gynak., vol. lii., 1896.
5 De Sinety, " Kecherches sur la muqueuse uterine pendant la menstrua-
tion," Annalcs de Gyncec., 1881.
6 Mandl, " Beitrag zur Frage des Verhaltens der Uterusmucosa wahrend
der Menstruation," Arch. f. Gynak., vol. lii., 1896.
7 Maerdervort, " Die normale und menstruirende Gebarmutterschleimhaut,"
Inorg. Dissert., Freiburg, 1895.
8 Champneys, " On Painful Menstruation," Harveian Lectures, 1890.
86 THE PHYSIOLOGY OF REPRODUCTION
Minot,1 and Martin,2 agree in supposing that the superficial
layers of the mucosa degenerate after the blood has passed out,
so that the bleeding is in no sense the consequence of the
destruction. According to Martin, fatty degeneration plays a
distinct part in causing the destruction.
Lipes has shown that the amount of destruction is related to
the character of the haemorrhage. If the congestion is rapid
and the amount of extravasated blood large, the denudation
FIG. 9 — Section through mucosa of human uterus showing sub-epithelial
hsematomata *. (From Sellheim.)
is comparatively extensive ; but if the haemorrhage is slight, and
takes place chiefly by diapedesis, then the loss of tissue is
practically nil. Lipes adds that in none of the cases examined
by him were there enough epithelial cells in the discharge to
suggest a complete loss of epithelium.
Galabin states that in addition to uterine and vaginal epithelial
cells being found in the discharge, shreds of tissue can frequently
be detected showing the structure of uterine stroma. Heape 3
1 Minot, loc. cit.
- Martin, " The Physiology of Ovulation, Menstruation, and Fertilisation,"
Hirst's Obstetrics, vol. i. 1888.
3 Heape, " The Menstruation and Ovulation of Monkeys and the Human
Female," Trans. Obstet. Soc., vol. xl., 1899.
CHANGES IN THE NON-PREGNANT UTERUS 87
also has detected stroma tissue in the menstrual discharge
of the human female. This clearly shows that destruction is
not always confined to the epithelial layer.
The blood poured out into the uterine cavity, and thence to
the exterior, does not usually clot, unless the amount be excessive.
This is due to the fact that the blood is considerably diluted
with mucus derived from the uterine glands. The glandular
activity is accompanied by an emigration of leucocytes which,
according to Blair Bell,1 are engaged in secreting calcium com-
pounds (see p. 69). The relative proportion of blood to mucus
I
• «*."* .-'' ' ' '->j> »*:• / .: •*''• --".^ •.'...;••-.",?. j<
:VMv:' -*$*' ' ,)-V
J^-y-% v^;£^--'--'$«.
m
P''i§iife^fe||§^l|^i
Uis^ is^ss^si
FIG. 10. — Section through mucosa of menstruating human uterus showing
bleeding into the cavity *. (From Sellheim.)
in the fluid is usually said to increase from the commencement
of menstruation, until the discharge reaches its maximum, after
which it goes on diminishing until the flow ceases.
The Stage of Repair. — This corresponds to .Gebhard's period
of post-menstrual involution. After the flow has ceased, or
even a shorf 'time before it has quite ceased, regeneration of the
uterine mucosa begins. According to Westphalen,2 profuse
karyokinesis takes place in the tissue of the mucosa, which once
more increases in thickness, whereas Heape, as will be seen
later, describes a shrinkage as occurring in the regenerative
1 Blair Bell, " Menstruation and its Relation to the Calcium Metabolism,"
Proc. Roy. Soc. Med., July 1908.
2 Westphalen, loc. cit.
88 THE PHYSIOLOGY OF REPRODUCTION
stage in monkeys. Wyder,1 who believed in the partial destruc-
tion of the uterine stroma, concluded that this was restored
by a hyperplasia of cells in the interglandular tissue of the
deeper layers of the mucous membrane, and that the lost epi-
thelium was regenerated from the epithelium of the glands.
Similar views have been held by other writers.
Those authorities who hold that the destruction is practi-
cally confined to the epithelium believe that the lost cells are
FIG. 11. — Section tbrough the human uterus during the recuperation
stage. (From Sellheim.)
replaced by multiplication of the remaining cells. Mandl, for
example, describes various stages of mitotic division in the
cells of the epithelium at this stage. But this author is of
opinion that the epithelia of the glands assist in the process of
renewal. Gebhard describes the epithelium, which had been
lifted from its bed by the blood in the hsematomata, as
sinking back to its former position, such cells as were lost
being regenerated by multiplication of the others.
The restoration of the mucosa is accompanied by a decrease
1 Whitridge Williams, loc. tit.
CHANGES IN THE NON-PREGNANT UTERUS 89
in the size of the blood-vessels, and an absorption of the blood
which remains extravasated in the stroma. As to how the
blood is absorbed has not been determined in the human female.
This is a question which will be discussed in considering the
regeneration stage in monkeys and in the lower Mammals. It
is stated that new capillaries are formed after the close of the
destruction.
The average length of the normal menstrual cycle, as already
mentioned, is twenty-eight days. Of these about five are
occupied by the pie-menstrual swelling, four by menstruation,
and probably about seven by the regeneration process, leaving
not more than twelve days for the period of quiescence.1 There
can be no doubt, however, that the length of the respective
stages must vary according to the extent of the destruction
and the amount of tissue which it is necessary to replace.
According to Westphalen,2 the regenerative process may last
for as long as eighteen days, or until the commencement of the
succeeding pre-menstrual swelling.3
THE CYCLE IN MONKEYS
The histology of the menstrual cycle in Semnopithecus
entellus and Macacus rhesus has been very fully studied by
Heape.4 Previously to Heape's work, Bland Sutton 5 had paid
some attention to the histology of the menstrual process in
Macacus rhesus, but without entering into great detail. More
recently van Herwerden 6 has given an account of the cyclical
changes of the uterus in Cercocebus cynomolgus.
1 Whitridge Williams, loc. cit.
2 Westphalen, loc. cit.
3 For further references to the subject of menstruation in the human
female the following authors may be consulted : Steinhaus, " Menstruation
und Ovulation," Leipzig, 1890; Heape, Phil. Trans. £., vols. clxxxv. and
clxxxviii., 1894 and 1897 ; Gebhard. " Die Menstruation," Veit's Handbuch
der Gynak., vol. iii., 1898. For an account of the various pathological changes
which are known to occur in the human uterus, see Macgregor, A Contribution
to the Pathology of the Endometrium., Edinburgh, 1905.
4 Heape, loc. cit.
5 Bland Sutton, "Menstruation in Monkeys," Brit. Gyncec. Jour., vol. ii.,
1880.
6 Van Herwerden, "Bijdrage tot de Kennis von den Menstrueelen
Cyclus," Tijdschrift d. Ned. DicrJc. Vereen., vol. x., 1906.
90 THE PHYSIOLOGY OF REPRODUCTION
Heape lias divided the cycle into the following four periods
and eight stages :—
B. Period of Growth. s
C. Period of Degeneration.
A. Period of Rest. Stage I. The Resting Stage.
/' , II. The Growth of Stroma.
III. The Increase of Vessels.
IV. The Breaking Down of
Vessels.
V. The Formation of Lacume.
VI. The Rupture of Lacume.
VII. The Formation of the
Menstrual Clot.
D. Period of Recuperation. „ VIII. The Recuperation Stage.
Heape's account may now be briefly summarised.
I. The Resting Stage. — The epithelial layer of the uterine
mucosa consists of a single row of cubical or columnar cells.
The outer border is clearly denned, but on the inner side the
protoplasm of the epithelium is continuous with that of the
sub-epithelial mucosa or stroma tissue. The surface epithelium
is continuous with that of the glands, but the latter rest on a
basement-membrane which separates them from the inter-
glandular stroma. The stroma contains round nuclei embedded
in a network of protoplasm, with fine, delicate processes in
which granules may be seen. In Semnopithecus fibrils running
fan-wise were observed in the deeper parts of the stroma, but
these were not seen in Macacus. Multiplication of cells was not
noticed at this stage, either in the epithelium or in the stroma.
The vessels in the mucosa are small. A few arteries occur in
the deeper portion, but only thin- walled capillaries in the more
superficial part ; the latter, however, are fairly numerous.
II. The Growth of Stroma. — The nuclei of the more superficial
part of the stroma undergo a great increase, the division being
amitotic in character, at least so far as could be seen. As a
consequence the mucosa in its upper third becomes considerably
swelled (hyperplasia), but in the deeper portion there is no
change in the tissue. Owing to the effects of pressure the
nuclei become elongated or fusiform. Division occurs either
by fragmentation or by the nucleus simply splitting into two.
The growth in the upper part of the stroma is associated with
an increase in the size of the blood-vessels in the deeper part.
CHANGES IN THE NON-PREGNANT UTERUS 91
The superficial epithelium, and also the epithelium of the glands,
remain practically unchanged.
III. The Increase of Vessels. — Owing to the continued swelling
of the stroma the nuclei in the superficial portion are packed
less densely, the lining epithelium becoming simultaneously
stretched. The glands tend to become wider. Hyperplasia
of the vessels occurs below the epithelium, the surface of
the mucosa appearing flushed. At the same time leucocytes
become more numerous within the vessels. There is no change
in the constitution of the deeper portion of the stroma.
IV. The Breaking Down of Vessels. — The whole of the
mucosa, including the epithelium, stroma, and vessel-walls, under-
goes pronounced hypertrophy, and in the superficial region the
congested capillaries break down and their contents become
extra vasated through the stroma. Fatty degeneration was not
observed byHeape, who is disposed to think that the degeneration
is of the amyloid or hyaline type. The leucocytes were noticed
to be increased decidedly in number, but they were only de-
tected outside of the blood-vessels in the superficial stroma,
where the vessel-walls had given way. Diapedesis of corpuscles
was nowhere observed. The nuclei of the stroma become larger
and more rounded, and exhibit a nuclear network and deeply
staining nucleoli. The glands increase in size, becoming longer ;
their lumina are wide, and an active process of secretion is
taking place. Superficially the mucosa appears very markedly
flushed.
V. The Formation of Lacunce. — At this stage the extravasated
blood corpuscles collect in lacunae which are situated in the
loose stroma tissue which lies below the epithelium. These
lacunae are clearly identical with the sub-epithelial hsematomata
of Gebhard. The dense stroma tissue, characteristic of an early
stage, still persists in places, but is now of rare occurrence. All
the superficial vessels have by this time broken down, but those
in the deeper tissue remain intact. Neither leucocytes nor red
corpuscles are to be found free in the deeper tissue of the stroma.
The condition of the glands is the same as in the preceding stage,
but there is evidence of degenerative changes in certain of the
stroma nuclei, and also in some of the free leucocytes.
VI. The Rupture of Lacunce. — The superficial stroma and
92 THE PHYSIOLOGY OF REPRODUCTION
epithelium shrivel up at this stage, and, as a consequence, the
blood contained in the lacunaB is poured into the uterine cavity.
The lacunse are very often close to the glands, so that when a
lacuna ruptures, a whole gland may be carried away in the
blood stream. The lacunae have no regular inner wall, but in
some places the processes of the stroma were observed to combine
together to form a kind of wall which appeared to resist the
further encroachment of blood corpuscles in the stroma tissue.
Leucocytes are very numerous (usually in the close neighbour-
hood of the ruptured vessels), some of them being described as
mononuclear, and some as having two, three, or four nuclei
(products of division). The proportion of leucocytes to red
corpuscles was found to be 2 per cent, of the former to 98 per
cent, of the latter in unruptured vessels full of blood, while in
ruptured vessels, from which blood had escaped, the percentage
of leucocytes was noted to be as high as 18*75. Heape does not
state, however, that basophil or eosinophil cells occur, such as
have been described in the uterus of the dog at a corresponding
stage in the cycle. Degenerative changes were noted in many
of the epithelial cells, and also in some of the stroma cells, certain
of which were seen scattered beneath the remains of the
epithelial lining. The stroma below the lacunae was observed to
contain normal as well as shrivelled tissue, but the deeper parts
appeared to undergo very little alteration.
VII. The Formation of the Menstrual Clot. — At this stage
Heape describes " a severe, devastating, periodic action/' The
entire superficial epithelium, portions of the glands or even a
whole gland, and a part of the stroma, with broken-down blood-
vessels and corpuscles, are torn bodily away, " leaving behind a
ragged wreck of tissue, torn glands, ruptured vessels, jagged edges
of stroma, and masses of blood corpuscles, which it would seem
hardly possible to heal satisfactorily without the aid of surgical
treatment/' Heape is in no doubt as to the extent of the
denudation, differing thus from those writers referred to above,
who believe that the destructive process in the human female
does not extend beyond certain portions of the superficial
epithelium. The cast-off mucous membrane is termed by
Heape the mucosa menstrualis. The deeper tissue undergoes
no change, the blood-vessels therein being still possessed of com-
CHANGES IN THE NON-PREGNANT UTERUS 93
plete walls, but these are larger and more numerous than before.
There is no extra vasated blood in this region. The proportion
of leucocytes in the vessels was observed to be about three
per cent, of the corpuscles present, while those on the surface "
were estimated to comprise about 2'5 per cent, of the total
number of corpuscles. Heape ascribes this comparative equalisa-
tion to the fact that the ruptured vessels to which the leucocytes
adhered in the earlier stages, are themselves cast off, and their
contents mingled with the extravasated blood. The supply of
leucocytes in the vessels, however, is well maintained.
The menstrual discharge is described as consisting of (1) a
viscid, stringy, opaque white fluid derived partly from the
blood serum and partly from the secretion of the uterine
glands, containing numerous small granules which have their
origin in the broken-down plasmodium of the uterine mucosa ;
(2) red blood corpuscles ; (3) masses of stroma tissue and
epithelium, both from the lining of the uterine cavity and from
the glands, and squamous epithelium from the vagina ; and
(4) leucocytes together with isolated nuclei of broken-down
epithelial and stroma cells. The menstrual clot is composed
very similarly, containing a mass of corpuscles together with
fragments of uterine tissue. It is expelled at the end of men-
struation after remaining some time in the uterine cavity.
VIII. The Recuperation Stage. — The changes which occur
during this stage are described by Heape as consisting of five
processes, as follows :—
(1) The re-formation of the epithelium.
(2) The reduction of the blood supply.
(3) The formation of new and recuperation of old
blood-vessels.
(4) The changes which take place in the stroma.
(5) The behaviour of the leucocytes.
(1) The new epithelium is formed, according to Heape, partly
from the epithelium of the glands, but partly from the underlying
stroma. The latter is described as a tissue of very primitive
characteristics, and the re-formation of the epithelium is re-
garded as a specialisation of cells belonging to a layer which, in
the embryo, gave rise in the same way to similar epithelial
94 THE PHYSIOLOGY OF REPRODUCTION
cells (that is to say, on this view, what takes place after men-
struation is merely a repetition of a process which occurs in the
embryo). The new epithelial cells, which are at first flattened,
gradually become cubical. Heape's account is thus completely
at variance with the descriptions of those authors who hold that
in the human female the epithelium is renewed entirely from
the torn edges of the old epithelium. Heape states that the
process of re-formation commences before the expulsion of the
menstrual clot, and even before the cessation of the flow of
blood into the uterine cavity.
(2) There is still an escape of blood as long as the menstrual
clot lies within the uterine cavity, but after its expulsion the
flow is checked. Heape suggests that the contractions of the
uterus which serve to expel the clot may assist in stopping the
escape of blood. Probably, also, the growth of the new epithelium
helps to stop the haemorrhage. After the growth of the new
vessels the flow of blood entirely ceases.
(3) At the commencement of this stage many of the ex-
tra vasated blood corpuscles are seen lying in intercellular spaces
in the stroma. These corpuscles, according to Heape, are drawn
again into the circulatory system by becoming enclosed within
newly formed capillaries. Heape describes the process as
follows : " The protoplasm of the cells bounding these [blood-
containing] spaces flattens out, the nuclei of the cells becoming
also flattened and elongated, and numerous fine capillary vessels
are thus formed, continuous with the deeper parts of the mucosa
with large prer-existing capillaries, and so with the circulatory
system.
" These fine capillaries exist only temporarily. When the
blood corpuscles are again drawn into the circulation, and when
the mucosa has shrunk again into its resting condition, the fine
capillaries are no longer seen ; but during the time in which
the reclaiming process goes on they exist in very large numbers/'
It should be added that this description of the formation of
vessels in the uterine mucosa of Semnopithecus and Macacus is
in opposition to the usual view regarding the growth of new
vessels, which are ordinarily supposed to be only capable of
developing as off-shoots from pre-existing ones.
K Heape also describes a recuperation of the old blood-vessels.
CHANGES IN THE NON-PREGNANT UTERUS 95
The nuclei which were hypertrophied become reduced in size,
and the swollen protoplasm becomes contracted. In this way
the vessels are reduced once more to their normal size.
(4) The changes in the cells of the stroma are described as
being similar to those in the cells which form the walls of the
hypertrophied vessels, the large nuclei and swollen protoplasm
giving place to compact nuclei and fine thread-like processes of
protoplasm. The multiplication of the stroma nuclei still goes
on to a limited extent, but is not nearly so frequent. The tissue
is very open during the early stages of recuperation, but
gradually becomes drawn together. As a result the whole
stroma is reduced considerably in bulk.
(5) The extravasated leucocytes, like the red corpuscles, are
said to be returned into the circulatory system by means of
the newly formed vessels. Heape says that isolated wandering
leucocytes are very rare indeed at this stage, and he makes no
mention of basophil or eosinophil cells, such as have recently
been described in the uterus of the dog. The actual proportion
of leucocytes within the vessels is said to be greater than at any
other period in the cycle, as many as fifty per cent, having been
observed in certain of the vessels. With regard to the function
of the leucocytes Heape suggests that in cases of suppressed
menstruation they might play an important part, but that in
normal menstruation " they seem to have been induced to
appear on the scene in such numbers, unnecessarily ; the casting
away of the menstrual mucosa, together with all noxious material,
and the clean healing of the wounded surface, rendering their
protective presence unnecessary." At the same time Heape
points out that the presence of the leucocytes in the vessels is
evidence of the existence therein of a noxious substance which
is not present in the surrounding tissue, and he supposes that
this irritant may be got rid of completely in the flow of blood.
Menstruation in Macacus has also been studied by Bland
Sutton,1 according to whom the sanguineous discharge is slight.
Button found no evidence of destruction of the uterine mucosa,
not even of the epithelium, but the uterus was distinctly con-
gested, and there was an escape of blood into the cavity. It
1 Bland Sutton, " Menstruation in Monkeys," Brit. Gyncec. Jour., vol. ii.
1880.
96 THE PHYSIOLOGY OF REPRODUCTION
should be noted, however, that Button's investigation was upon
monkeys in this country, whereas Heape's observations relate to
Indian animals, and that in Pocock's experience,1 menstruation
does not, as a rule, occur in Macacus rhesus in the Zoological
Gardens. But it would appear also from this author's observa-
tions that the severity of the menstrual process in monkeys may
vary within as wide limits as it is said to do in the human female.
The changes which occur throughout the menstrual cycle in
Cercocebus cynomolgus have been studied in some detail by
van Herwerden,2 who begins by classifying the material in two
groups. In group A are included those animals in which, at the
time of killing, the uterus was relatively small and menstrua-
tion was correspondingly slight. In group B are placed those
monkeys which, on being killed, showed comparatively large
well-developed uteri, and in which the menstrual process was
characterised by some degree of severity. Van Herwerden is of
opinion that the individuals included in the first category were
animals killed during the non-breeding season, while those be-
longing to group B were specimens killed at the breeding season,
when the generative organs were in a state of greater activity.
The complete menstrual cycle in Cercocebus is divided into
the following periods and stages :—
I. Inter-menstrual period.
f 1. Increase of superficial stroma elements.
II. Pre-menstrual period . Q1. ,, „. .
v2. Slight swelling of mucosa.
1. Increasing hypersemia.
2. Rupture of capillaries.
3. Formation of lacunae.
TTT , , 4. Degeneration of epithelium and stroma
III. Menstrual period . •
elements.
5. Rupture of lacunre and tearing off of
degenerate tissue.
§. Beginning of regeneration.
IV. Post-menstrual period.
It will be seen from this scheme of classification that the
changes recorded by van Herwerden as occurring in the
menstrual cycle of Cercocebus are very similar to those described
1 Pocock, "Notes upon Menstruation," &c., Proc. Zool. Soc., 1906.
2 Van Herwerden, loc. cit.
CHANGES IN THE NON-PREGNANT UTERUS 97
by Heape in Semnopithecus and Macacus. Both authors agree
in stating that the superficial portion of the mucosa is denuded
during the destruction period, differing thus from Bland Button
and those writers on human menstruation (referred to above)
who maintain that the denudation only involves certain portions
of the superficial epithelium. Van Herwerden states that the
menstrual changes are less marked in the region of the fundus
uteri.
The chief differences between van Herwerden's account and
that of Heape are as follows :— -.
According to the former the stroma cells increase mitotically,
and not by simple division or fragmentation as supposed by
Heape.
The epithelium is described as being renewed from the
glandular epithelium in Cercocebus, and not in part from the
subjacent stroma, as it is said to do in Semnopithecus and
Macacus.
Van Herwerden says that, so far as was observed, the walls
of new vessels were not formed during recuperation from
stroma cells, as has been described by Heape.
Van Herwerden states that Cercocebus may experience
oestrus after menstruation is over. Presumably, therefore,
oestrus occurs contemporaneously with the recuperation process
in the uterus.
THE CYCLE IN LEMURS
As already mentioned, Stratz 1 has called attention to the
prooostrous changes which take place in the uterus of Tarsius
spectrum,, but the process has been studied more closely by van
Herwerden.2 This author describes the following changes : —
(1) There is a swelling of the glands which is closely followed
by mitotic division among a large number of the epithelial cells.
Hypersemia then sets in ; but the congestion is localised to
certain places, and is not diffused over the entire mucous mem-
brane. Afterwards blood becomes extra vasated in the stroma
tissue, the corpuscles being aggregated in the more superficial
parts — that is to say, in the vicinity of the epithelium. It was
1 Stratz, Dcr ycschlcchtsrc ife Saiiyethiereierstocl:, Haag, 1898.
2 Van Herwerden, loc. cit.
98 THE PHYSIOLOGY OF REPRODUCTION
noticed that certain corpuscles were taken up by leucocytes,
and transported to the uterine cavity. Others were carried
along in close association with epithelial cells, both from the
superficial layer and from the glands.
It would appear that destruction of the epithelium does
not occur to any extent, and that the bleeding is not severe.
This would seem to constitute the chief difference between the
prooestrous changes in Tarsius, and the corresponding changes
in monkeys.
The periodicity of the sexual phenomena in Tarsius spectrum
has already been referred to.
THE CYCLE IN INSECTIVORA
The changes which occur in the internal generative organs
during the cycle in Tupaia javanica, and in the aberrant In-
sectivore, Galeopithecus volans, have received some slight
attention.
Stratz 1 has described the existence of a blood-clot and a
" menstrual " flow in Tupaia, and records the presence of
desquamated epithelial cells in the blood-clot. Van Herwerden,2
however, states that the individuals which Stratz examined
were in the puerperal stage, and that, although Tupaia can ex-
perience " heat " and become pregnant at this time, trust-
worthy conclusions regarding the severity of the prooestrous
changes cannot be drawn from such specimens. That there
was considerable bleeding van Herwerden admits. Nothing is
known about the periodicity of the changes in Tupaia.
In Galeopithecus van Herwerden describes uterine hyper-
aemia during the prooestrum. In the superficial mucosa
numerous highly congested "capillaries were noticed. In the
later stages blood was found extra vasated in the stroma, some
of it being collected in spaces which were probably comparable
to the sub-epithelial hsematomata described by Gebhard in the
menstruating human female. In the superficial epithelium
spots were detected where a few of the cells had been removed.
Bleeding did not appear to be localised to any particular area
in the uterus.
1 Stratz, loc. cit. 2 Van Herwerden, loc. cit.
CHANGES IN THE NON-PREGNANT UTERUS 99
Van Herwerden is certain that the changes observed could
not be ascribed to a puerperal condition, as in the case of Tupaia,
but must have been the result of a normal proosstrum. The
periodicity of the changes is unknown.
THE CYCLE IN CARNIVORES
The histological changes in the non-pregnant uterus have
been studied in the dog 1 and in the ferret.2 The periods into
which the uterine cycle is divided are identical with those
adopted by Heape for the monkey :—
(1) Period of rest Anoestrum.
(2) Period of growth and congestion . ) Prooestrum.
(3) Period of destruction . )
( (Estrus.
(4) Period of recuperation . . ' j M t t
It is seen that oestrus, or the time of desire, begins normally
about the close of the period of destruction. With the ferret
it may be very prolonged, extending until the end of the
recuperation period, or even considerably beyond it. Conse-
quently there may be no metcestrum (strictly speaking) with
the ferret, since the period during which copulation can occur
is liable to persist until the uterus has reached the resting stage.
(1) Period of Rest. — The uterine mucosa in both the dog and
the ferret is bounded at the surface by an epithelium consisting
of a single row of columnar or cubical cells, and is continuous
with that of the glands. The stroma is a connective tissue,
containing numerous fusiform cells. Blood-vessels of small
size are fairly common. Leucocytes do not appear to occur in
the mucosa outside of the vessels. Pigment is not present at
this stage, at least ordinarily.
(2) Period of Growth and Congestion. — The mucosa at this
period becomes slightly thickened, and tends to be more compact.
This is effected by cell divisions, but mitoses have not been
1 Marshall, and Jolly, " Contributions to the Physiology of Mammalian
Reproduction: Part I. The (Estrous Cycle in the Dog," Phil. Trans., B .,
vol. cxcviii., 1905.
2 Marshall, " The (Estrous Cycle in the Common Ferret," Quar. Jour. Micr.
Sci. vol. xlviii., 1904.
100 THE PHYSIOLOGY OF REPRODUCTION
observed. Retterer,1 who has contributed a short account of the
changes in the bitch's uterus, describes the mucosa as growing
to three or four times its normal thickness, but this observation
has not been confirmed. The growth is accompanied by en-
largement and congestion of the capillaries, which at the same
time become more numerous.2 The vessels in the surrounding
muscular tissue also tend to enlarge. The epithelium undergoes
°
• * *«g«3Wi s 9 #*&>\*g¥$f ~ ** •?? '.£*" !£
* V!*?^f s^ " *'*> ***&*"'
««VtWW
•?""* .:?." "Cj
-,sF^'
FIG. 12. — Section through prooestrous uterine mucosa of dog, showing
congested vessels between the glands. (From Marshall and Jolly.)
no material change so far as seen. In the case of the ferret the
uterine cavity is described as becoming markedly reduced in
size, while the glands are stated to undergo an appreciable
swelling accompanied by an increased secretory activity.
(3) Period of Destruction. — The walls of the stretched blood-
vessels break down, and red corpuscles, accompanied by
1 Retterer,- " Sur les Modifications de la Muqueuse Uterine a 1'Epoque
du Rut," C. R. de la Soc. de BioL, vol. iv., 1892.
2 Of. Retterer, loc. cit. ; also Keiffer, "La Formation Glandulaire de
1'Uterus," Annales de la Soc. Medico- Chirurg. de Brabant, 1899; and Bonnet,
" Beitragerzur Embryologie des Hundes," Anat. Hefte, vol. xx., 1902.
CHANGES IN THE NON-PREGNANT UTERUS 101
leucocytes, become extravasated throughout the stroma. Some
of the vessels, however, remain intact. The breaking down of
vessels appears to occur fairly uniformly throughout the stroma
instead of being restricted to any particular portion. The
extravasated blood for the most part collects immediately below
the superficial epithelium, but it is not aggregated in large
lacuna-like spaces, such as Heape has described in the monkey.
polyrr/ }®*jfa
V*!? * * * * * •*
ex. bl.
w
FIG. 13. — Section through prooestrous uterine mucosa o£ dog. (From
Marshall and Jolly.)
ex. bl., Extravasated blood corpuscles ; polym., polymorph ; sec., cells
probably indicating secretory activity.
These " sub-epithelial hsematomata " have been noticed espe-
cially in the procestrous bitch. The walls of the vessels in the
muscular layers do not give way.
Eventually the extravasated blood corpuscles (or, at any
rate, the majority of them) make their way into the cavity of
the uterus, and thence to the vagina, where external bleeding is
observed. This is especially noticeable in the case of the bitch,
with which, as already mentioned, external bleeding may last
for as long as ten days. The bleeding is accompanied by an
increase in the mucous secretion. At about the same stage
102 THE PHYSIOLOGY OF REPRODUCTION
goblet-shaped cells are frequently observable in the glandular
epithelium, and it is suggested that these are in some way con-
nected with the secretory activity of the glands.
It is probable that destruction of the superficial epithelium
occurs normally to a greater or less extent both in the bitch and
in the ferret. Epithelial cells have been observed lying free in
the uterine cavity, while, in some sections, places have been
noticed where the stroma presented a raw edge, having been
stripped of its epithelial covering. In the bitch a layer of
flattened stroma cells may sometimes be seen in close attach-
ment to the epithelium during the process of denudation. In
the ferret it would appear that the destruction may occasionally
be severer, but it is thought that this is exceptional. It has
been pointed out, however, that a comparison between the
thickness of the uterine wall (and conversely the size of the
uterine cavity) in ferrets killed at the commencement of the
recuperation period and during the period of rest, is very sug-
gestive of a definite removal of stroma as well as of epithelium
in the process of destruction.
Polymorph leucocytes have been observed in abundance
at this stage in the bitch's uterus, both in the stroma and also
in the cavity, and large mononuclear leucocytes (hyaline cor-
puscles), containing pigment derived doubtless from the ex-
travasated blood, have also been seen to occur. Large cells,
with faintly staining nuclei of very considerable size and con-
spicuous nucleoli, have been noticed at rare intervals lying in
spaces in the stroma tissue of the procestrous bitch. The origin
and significance of these cells are not known.
There is no blood-clot formed in the uterus, either in the
bitch or in the ferret.
(4) Period of Recuperation. — The new epithelium in the bitch
is first seen as a layer of flattened cells which bear a resemblance
to the cells of the stroma. Its manner of formation is an open
question, but it would seem probable that it is derived mainly,
if not entirely, from the remaining cells of the old epithelium, or
from those of the glands. It is just possible, however, that
in certain places the epithelium may be renewed from the
underlying stroma tissue, as is said by Heape (but no.t by van
Herwerden) to be the case in the monkey.
CHANGES IN THE NON-PREGNANT UTERUS 103
During the earlier stages of recuperation a variable, and
often a large, number of red blood corpuscles remain scattered
in the stroma, chiefly in the part nearest the surface. At a
later stage extravasated corpuscles are no longer seen in any
quantity, while numerous new vessels appear to have been
formed, presumably from pre-existing vessels.
Polymorphs are no longer common in the bitch's mucosa
tissue, but leucocytes of other varieties are a characteristic
polym.
©
silo.
bl. v.
pg,
FIG. 14. — Section through edge of mucosa of dog during an early stage
of recuperation. (From Marshall and Jolly.)
bl. v., blood-vessel ; ep., epithelium in process of renewal ; piy., pigment;
polym., polymorph.
feature. The following kinds have been observed : (1)
Coarsely granular eosinophil cells, with lobed nuclei. These
occur in the blood in cases of trichinosis, bronchial asthma,
sarcoma, osteomalacia, skin diseases, and other affections, but
are rare under ordinary conditions. (2) Basophil cells, with
simple nuclei and containing coarse granules, but never any
pigment. The number of granules varies, and in some of the
cells is very small. These basophil cells are evidently similar
to the mast cells of Ehrlich, and the plasma cells of Unna. Mast
104 THE PHYSIOLOGY OF REPRODUCTION
cells are said to be often found in inflammatory areas, and are
described as occurring in the stroma tissue of tumours in asso-
ciation with plasma cells, and also in the peripheral circulation
in cases of lymphatic and myeloid leucaemia. They are
especially numerous during the recuperation period of the
bitch's uterus, and it is suggested that they must in some
unknown way be functionally connected with that process.
eos.
sir.
FIG. 15. — Section through portion of mucosa of dog during the recupera-
tion period. (From Marshall and Jolly.)
bas., basophil cell ; eos., eosinophil cell ; raon., mononuclear leucocyte ;
polym., polymorphs ; str., stroma cell.
(3) Large mononuclear leucocytes (hyaline corpuscles or macro-
cytes), containing blood-pigment which gives the Prussian-blue
reaction. Since pigment formation and ingestion by leucocytes
are of frequent occurrence in the bitch's uterus at about
this stage, it is probable that this is the fate of the great
majority of the extra vasated red corpuscles. It is possible,
however, as suggested in the paper from which this account is
taken, that a relatively small proportion may make their way
CHANGES IN THE NON-PREGNANT UTERUS 105
into the lymphatics, and so re-enter the circulation. Pigment
formation has not been observed in the ferret.
At a late stage in recuperation the stroma tissue tends to
become denser, and also to increase in thickness (ferret), until
the whole uterus once more acquires its normal condition.
If copulation has taken place, spermatozoa in great numbers
sp.
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FiG. 16. — Section through mucosa of dog during a late stage of recupera-
tion. (From Marshall and Jolly.)
II. v., blood-vessel; sp., spermatozoa in cavity of gland.
may be observed in the deeper portions of the uterine glands,
as well as along the edges of the uterine cavity.
THE CYCLE IN RODENTS
Comparatively little attention has been paid to the uterine
changes in Rodents. In the rabbit it has been noticed
that the uterus is swollen and congested during^ " heat/'
and the same observation has been made in the marmot
106 THE PHYSIOLOGY OF REPRODUCTION
(Spermophilus citillus).1 Lataste 2 has described prooestrous
growth and congestion in the uterus of several Mnridae,
and this is stated to be followed by a sanguineous dis-
charge from the original opening. Lataste has also described
desquamation of the uterine epithelium, but he appears to
regard this process as taking place independently of " heat/'
More recently Konigstein 3 has recorded cyclical changes in
FIG. 17. — Section through portion of prooestrous uterine mucosa of
rabbit showing glandular activity. (From Blair Bell, in Proc.
Roy. Soc. Medicine.)
several Rodents (rat, guinea-pig, &c.), and has described
prooestrous desquamation of the uterine epithelium, followed
by recuperation. The degenerative changes are accompanied
1 Eejsek, " Anheftung( Implantation) des Saugethieres an die Uteruswand,
insbesondere des Eies von Spermophilus citillus," Arch. f. Mikr. Anat., vol. Ixiii.,
1904.
2 Lataste, Recherches de Zoethique sur Us Mammiferes de I'ordre des Ronycurs,
Bordeaux, 1887.
3 Konigstein, '-Die Veranderungen der Genitalschleimhaut wahrend der
Graviditat und Brunst bei einigen Nagern," Pjlugers Arch., vol. cxix., 1907.
CHANGES IN THE NON-PREGNANT UTERUS 107
by a secretion of mucus, and there is a marked leucocytosis
over the entire generative tract. Desquamation of epithelium
also occurs in the vagina. Furthermore, emigration of leucocytes
between the epithelium of the glands, accompanied by great
glandular activity, has been observed by Blair Bell 1 in the
prooestrous uterus of the rabbit.
THE CYCLE IN UNGULATES
The uterine changes have been worked out most fully in
the case of the sheep.2 They relate chiefly to the blood-vessels,
and are grouped according to four periods as in the case of
the monkey, the dog, and the ferret, referred to above.
(1) Period of Rest. — The histological characters of the uterus
during this period are those of an organ in a state of quiescence.
Protoplasmic processes can be seen passing from certain of the
stroma nuclei, but these, though denser in some places than in
others, show little evidence of division. Dark brown or black
pigment may be present in considerable quantities, especially in
the region subjacent to the epithelium, both in the cotyledonary
papillae and (more frequently) between them and round their
bases. Such pigment has not been observed in yearling sheep
(i.e. in sheep less than a year old) ; neither does it appear to
occur, as a rule, during the anoestrum, but only during the
dices trous interval.
(2) Period of Growth. — The nuclei in the stroma multiply,
and the mucosa increases slightly in thickness. The epithelium,
however, appears to remain unaffected. The blood-vessels in-
crease both in size and number, producing uterine congestion.
These changes occur both in the cotyledonary papillae and in
the intervening tissue around the bases of the papillae.
(3) Period of Destruction. — The congestion is followed in most
cases by the breaking down of some of the vessels. Very fre-
quently the first extravasation takes place from vessels situated
immediately below certain parts of the stroma where the nuclei
are most thickly distributed. Leucocytes are extra vasated
1 Blair Bell, loc. cit.
2 Marshall, "The (Estrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans., B., vol. cxcvi., 1903.
108 THE PHYSIOLOGY OF REPRODUCTION
along with the red corpuscles, but there is no evidence of the
existence of wandering cells apart from those which are derived
apparently from the broken-down vessels. The blood tends to
collect below the epithelium. Bleeding into the uterine cavity
may occur, but is not invariable. A few epithelial cells are
sometimes torn off (presumably in places where blood is poured
out into the cavity), but destruction even to this extent does not
necessarily take place. Denudation of the stroma has never
been observed. It would seem that the severity of the pro-
cestrous process tends to diminish with each successive dioestrous
cycle in the breeding season, and that sometimes in a late
procestrum the period of destruction is never reached, the
congested vessels subsiding without undergoing rupture. Bleed-
ing, when it does occur, appears to be more frequent in the
cotyledonary papillae than between them, and is commoner in
the large papillae than in the smaller ones.
Kazzander 1 appears to have been the first to detect ex-
tra vasated blood in the sheep's mucosa. Subsequently Bonnet 2
has noted uterine bleeding in various Ruminants, as well as in the
mare and sow, and Kolster 3 has made similar observations
(cf. also Emrys-Roberts, see p. 47). Ewart also has described
procestrous extravasation and the presence of haBmatoidin
crystals in the uterus of the mare. Glandular activity during
heat was also noted.4
(4) Period of recuperation. — The sheep's prooestrum may be
said to end with the period of destruction, the entire process
probably lasting for not longer than one or two days, its exact
duration depending upon its severity. (Estrus itself, which
occurs during the beginning of the period of recuperation, some-
times occupies only a few hours.
In those places where bleeding into the cavity took place in
the preceding period the epithelium is renewed, apparently
1 Kazzander, " Uber die Pigmentation der Uterinschleimhaut des Schafes,"
Arch.f. Mikr. Anat., vol. xxxvi., 1890.
2 Bonnet, article in Ellenberger's Vergleichende Physiologic des Haussduge-
thicre, vol. ii., Berlin, 1892. Cf. also Ellenberger's article in same volume.
3 Kolster, " Weitere Beitriige zur Kenntniss der Embryotrophe bei Indeci-
dunten," Anat. Hefte, vol. xx., 1902.
4 Ewart, " The Development of the Horse," Quar. Jour. Micr. Science,
(not yet published).
CHANGES IN THE NON-PREGNANT UTERUS 109
from the edges of the adjoining epithelium which had not
suffered destruction. In this way the re-formation of the
epithelium is sufficiently accounted for, since, as already re-
marked, only a very inconsiderable number of cells is removed
during the sheep's prooestrum.
Congestion of the stroma gradually diminishes, and the
pig.
l
m
•>'-'',\«^-.-"^k. /- : ', •.&;.,- • •-*<
FIG. 18. — Section through portion of uterine mucosa of sheep showing
black pigment (pig.) formed from extravasated blood.
mucosa as a whole undergoes a slight shrinkage. It would
appear that a few new capillaries are formed, but there is no
evidence that any of the extravasated corpuscles are gathered
up afresh into the circulatory system. On the other hand,
there are ample indications that all those corpuscles which
remain in the tissue become transformed into pigment, as
originally concluded by Bonnet.1 According to this investigator,
the extravasation takes place in the deeper mucosa, and the
1 Bonnet, " Uebcr Melanose der Uterinschleimhaut," &c., Deutche Zeitsch.
f. Thicrmedizin, vol. v., 1880, and vol. vii., 1882. "Beitrage zum Embryologie
der Wiederkauer," &c., Arch. f. Anat. u. Phys., Anat. Abth., 1884.
110 THE PHYSIOLOGY OF REPRODUCTION
derivatives of the corpuscles are carried in the form of pigment
to the more superficial area by wandering cells. Kazzander,1
however, does not admit the agency of leucocytes ; but the most
recent observations support Bonnet's conclusions, excepting
that (as previously stated) the extravasation which takes place
during the destruction period is in the superficial mucosa rather
than in the deeper tissue. Thus, although leucocytes are pro-
bably involved in the process of pigment formation, there is no
need to assume that they carry the extravasated corpuscles to
the region where pigment is most abundant. Sometimes the
interior of the uterus appears superficially to be perfectly black
with pigment, but in such cases the pigment is, no doubt, de-
rived from blood which had been extravasated during a series
of prooestrous periods, and not merely during the most recent one.
Assheton 2 states that the pigment so formed is subsequently
disposed of.
A consideration of the facts set forth in this chapter should
leave one in no doubt regarding the essential similarity between
the menstrual cycle in the Primates, and the cestrous cycle in
the lower Mammalia. Those who have denied that there is any
correspondence between " heat " and menstruation 3 have laid
stress upon the assertion that whereas " heat " in the lower
animals is the time for coition, this act, as a general rule, is not
performed during menstruation. But, as was first pointed out
by Heape, it is the prooestrum alone and not the entire " heat
period " (a term used generally to include both prooestrum and
oestrus) which is the physiological homologue of menstruation ;
and, moreover, the latter process in many of the Primates is
succeeded by a regular post-menstrual oestrus.
The physiological identity of the procestrum with menstrua-
tion should always be kept in view in considering the cause and
nature of the phenomena, since, as will be seen later, many
strange errors have been committed, and wrong conclusions
1 Kazzander, loc. cit.
2 Assheton, "The Morphology of the Ungulate Placenta," Phil. Trans.
B., vol. cxcviii., 190G.
3 Beard, in The Span of Gestation and the Cause of Birth (Jena, 1897),
says, " very little is required in disproof " of this correspondence.
CHANGES IN THE NON-PREGNANT UTERUS 111
arrived at, through failure to realise the unity of the two pro-
cesses.
It has been shown further that although the changes which
occur in the uterus during the cycle present a striking similarity
in the various mammalian types in which they have been
studied, yet there, is a considerable amount of variation in the
severity and duration of the prooestrous phenomena. The
extent of the congestion, and the destruction which usually
succeeds it, are greatest, as a rule, in the highest Mammals,
and comparatively slight in the Rodentia and Ungulata. The
histology of the cycle in the lowest Mammals has never been
worked out, but, as already mentioned in the preceding chapter,
vaginal bleeding has been noticed in Marsupials.
The purpose or meaning of the procestrum, and the factors
which contribute to its occurrence, will be considered as fully
as the present knowledge of the subject permits, after the changes
which take place in the ovaries have been dealt with, in a future
chapter of this work. It may be at once stated, however, that
most authorities are now agreed that the menstrual process is in
some sense a preparation for the attachment of an ovum to the
wall of the uterus, but opinions differ as to the precise nature of
the preparation. On the other hand, it is evident that the
changes involved in menstruation are not absolutely essential,
since there are records of pregnancy occurring in individuals
who had never experienced menstruation. Moreover, there is
evidence that the prooestrous discharge may be not only of no
utility to the organism, but may even become injurious, as in
the more severe cases of menstruation among women.
In view of these facts it may be called in question whether
the procestrous changes in the uterus should not be regarded
merely as the result of a wave of disturbance which ushers in the
period of desire, and is of the nature of a consequence rather
than a purpose. This is in accord with MetchnikofTs suggestion,1
that the catamenia in women is essentially a " disharmony " of
organisation, which has been brought about as the result of
modifications acquired recently in the history of the species.
If this is so, a similar explanation must be adopted in the case of
1 Metchnikoff, The Nature of Man, Mitchell's Translation, London
1903.
THE PHYSIOLOGY OF REPRODUCTION
those animals which experience an especially severe prooestrum.
According to such a view as this the phenomena of menstruation
must be looked upon as belonging to the borderland of pathology.
In this connection the large number of leucocytes which attend
the menstrual process, some of them clearly phagocytic in
function, is not altogether unsuggestive.
CHAPTER IV
CHANGES IN THE OVARY— OOGENESIS— GROWTH OF FOL-
LICLES—OVULATION— FORMATION OF CORPORA LUTEA
AND ATRETIC FOLLICLES— THE SIGNIFICANCE OF THE
PROOESTROUS CHANGES IN THE UTERUS
" The newest freak of the Fallopian tubes and their fimbrise, and the
very latest news from the ovisac and the corpora lutea." — JOHN BROWN,
Jlorce Subsecivce.
DEVELOPMENT OF OVARY AND OOGENESIS
THE animal egg is a large spheroidal cell consisting of external
protoplasm or cytoplasm, a nucleus or germinal vesicle, and a
nucleolus or germinal spot.1 Within the cytoplasm is a mass of
food material or yolk (sometimes known as deutoplasm), the
quantity of which varies slightly in different Mammalia, and is
very considerable in birds and certain other animals. The
unfertilised ovum differs from the male germ-cell or spermatozoon
in its devoting itself mainly to the storage of food-substance and
accumulation of potential energy, for it is incapable of active
movement. The metabolic processes of the ovum, therefore, are
almost entirely constructive, while those of the spermatozoon
are largely destructive. The function of the ovum is to con-
jugate with the spermatozoon, and subsequently, by a lengthy
process of cell division, to give rise to a new individual.
The mammalian ovary,2 or organ in which the ova are pro-
duced, is composed of a stroma of fibrous connective tissue,
which contains some plain muscular fibres (especially in the
neighbourhood of the attachment to the broad ligament) as
well as numerous blood-vessels. The surface is lined by a
layer of columnar epithelial cells. Within are a number of
1 A centrosome has been described as present in the ova of some animals.
For a detailed description of the ovum in different forms see Wilson, The
Cell in Development and Inheritance, 2nd Edition. New York, 1900.
2 See also Stratz, Der geschlechtsreife Sdugethiereierstock, Haag, 1898.
113
114 THE PHYSIOLOGY OF REPRODUCTION
vesicles of various sizes, each with an ovum, surrounded by an
epithelium. These are called Graafian follicles. Certain other
structures, consisting of very large yellow-coloured cells en-
closed by a branching network of connective tissue, are also
often found. These are the corpora lutea or discharged follicles
to be described more fullv later. The stroma contains, further,
a varying number of epitheloid interstitial cells.
In order to gain a proper understanding of the structural
i
FIG. 19.— Section through ovary of cat. (From Schron.)
1, Outer surface; I/, attached border; 2, fibrous central stroma; 3, peri-
pheral stroma ; 4, blood-vessels ; 5, young follicles ; 6, 7, 8, 9, and 9',
larger developing follicles ; 10, corpus luteum.
and functional relations of the different parts of the ovary,
it is necessary to make some study of its developmental history.
Pfliiger 1 appears to have been the first to regard the ova 2
and epithelial cells of the Graafian follicles as originating either
in the form of ingrowths simulating tubular glands, or as solid
columns of cells from that embryonic layer which Waldeyer
afterwards designated the germinal epithelium. The tubular
ingrowths had already been noticed by Valentin,3 who, however,
1 Pfliiger, Ueber die Eierstocke der Sdugethiere und dcs Menschcn, Leipzig,
1867.
2 The mammalian ovum was discovered by von Baer (Ueber EntwicJcc-
lungsgeschichte der Thiere-Beobachtung und Reflexion, vol. i., Konigsberg, 1828).
In 1861 Gegenbaur showed that the vertebrate ovum was a single cell.
3 Valentin, " Ueber die Entvvickelung der Follikel in dem Eierstocke der
Saugethiere," Milller's Arch., 1838.
CHANGES IN THE OVARY
FiG. 20. — Section through ovary of adult dog. (From Waldever.)
a, germinal epithelium ; 6, remains of egg tubes; c, small follicles ; d, more
advanced follicle ; e, discus proligerus and ovum ; /, second ovum (a rare
occurrence) ; f/, theca externa of follicle ; A, theca interna ; i, membrana
granulosa ; k, degenerate follicle ; I, blood - vessels ; m, tubes of
parovarium ; y, involuted germinal epithelium ; 2, transition from
germinal to peritoneal epithelium.
failed to recognise their connection with the germinal epithelium.
Later observers, however, did not confirm the tubular origin of
the ovary.
To Waldeyer belongs the credit of first recognising the true
nature and significance of the process of egg formation, an
116 THE PHYSIOLOGY OF REPRODUCTION
account of which was published in his famous monograph
Eier stock und Ei.1 He found that in the chick, on the fourth
day of development, the coelomic epithelium which covers
the inner surface of the Wolffian body became differentiated
from the tissue surrounding it, the cells being relatively large
and cuboidal in shape. A little later he observed that the cells
had multiplied to such an extent as to give rise to a distinct
elevation. In this way the germinal epithelium was formed,
and this marked the site of the future ovary. The mesoblast
underlying the germinal epithelium is described as growing
upwards among the cells of the latter, and so giving rise to the
FIG. 21. — Section through ovary of pig embryo. (From Williams'
Obstetrics, Appleton & Co.)
G.E., germinal epithelium ; S., stroma.
appearance of those germinal ingrowths or " egg- tubes/' which
were described by Pfliiger.
The cells of the germinal epithelium are thus divided by
mesoblast into clusters of " egg-nests " which contain the pri-
mordial ova, as Waldeyer has shown. As a result of this process
two zones of tissue are formed in the future ovary. The outer
or cortical zone consists of clusters of cells derived from the
germinal epithelium, with mesoblastic processes in between
them. The inner or medullary zone is composed at first entirely
of mesoblast, which gives rise to the vascular tissue and stroma
of the ovary.
The majority of investigators, including Balfour,2 Schafer,3
1 Waldeyer, Eierstock und Ei, Leipzig, 1870.
2 Balfour, " Structure and Development of the Vertebrate Ovary," Quar.
Jour. Micr. Science, vol. xviii., 1878.
3 Schafer, "On the Structure of the Immature Ovarian Ovum,"&c., Proc.
Roy. Soc., vol. xxx., 1880.
CHANGES IN THE OVARY 117
Nagel,1 and van Winiwarter,2 have followed Waldeyer in suppos-
ing that the follicular epithelial cells (which form the innermost
layer of the wall of the Graafian follicle) are derived like the ova
from the germinal epithelium. Schafer described appearances
indicating the possibility of the innermost layer of follicular
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m
r'
FIG. 22. — Cortex of pig embryo, showing germinal epithelium, Pfluger's
tubes with ova in various stages of development. (From Williams'
Obstetrics, Appleton & Co.)
epithelium being derived from the ovum itself ; but, as he himself
pointed out, this view does not involve any morphological ab-
surdity if the ova and follicle-cells have a common origin. Balfour
described protoplasmic masses of embryonic ova in which the
cells appeared to be united together in such a way as to suggest
1 Nagel, " Das menschliche Ei," Arch. f. Mikr. AnaL, vol. xxxi., 1888.
2 Van Winiwarter, " Recherches sur 1'Ovogenese," &c., Arch, de Biol,,
vol. xvii., 1901.
118 THE PHYSIOLOGY OF REPRODUCTION
that one ovum might undergo development at the expense of the
others. Somewhat similar appearances have been observed in
the bat's ovary by van Beneden,1 who regarded them as syncitia
from which both ova and follicular epithelial cells took origin.
On the other hand, KoUiker believed that the follicle-cells
arose from the epithelium of the Wolffian body, while Foulis,2
Schron,3 "Wendeler,4 and Clark,5 expressing the opinion that the
follicle-cells are derived from the mesoblast, have also dissented
from this the more usual view. Clark, in support of his theory,
has pointed out that the cells which immediately surround the
primordal follicles are often spindle-shaped and similar in ap-
pearance to many of the stroma cells, and further, that the
primordal ova in the early stages of development are often
apparently in direct contact with connective tissue which
obviously had been derived from the embryonic mesoblast.
Most authorities, however (including the more recent in-
vestigators), are of opinion that the follicular epithelial cells,
in common with the ova, are derived from the germinal
epithelium. Further, Miss Lane-Clay pon 6 has recently shown
that the epithelioid interstitial cells 7 which (in addition to the
connective tissue and plain muscle-fibres) are contained in the
ovarian stroma in all probability arise also from the original
germinal epithelium.
The changes involved in the production of ova have been
fully investigated by van Winiwarter 8 in the rabbit. These
1 Van Beneden and Julin, " Observations sur la Maturation," &c., Arch, de
Bid., vol. i., 1880.
2 Foulis, "The Development of the Ova," &c., Jour. Anat. and Phys.,
vol. xiii., 1876.
3 Schron, " Beitrag zur Kenntniss der Anatomie und Physiologic des
Eierstocks der Saugethiere," Zeitscfi.f. wisscnsch. Zool., vol. xii., 1863.
4 Wendeler, " Entwickelungsgeschichte und Physiologic der Eierstocke,"
Martin's Die Krankheiten des Eierstocks und Nebeneierstocks . Leipzig 1899.
5 Clark, "The Origin, Growth, and Fate of the Corpus Luteum," Johns
Hopkins Hospital Reports, vol. vii., 1898.
6 Lane-Claypon, " On the Origin and Life History of the Interstitial Cells
of the Ovary of the Rabbit," Proc. Roy. Soc., £., vol. Ixxvii., 1905.
7 For a comparative account of the interstitial substance in the ovaries of
various mammals, with references to the literature, see Fraenkel, " Vergleichende
Histologische Untersuchungen iiber das Vorkommen driis'iger Formationen im
Interstitiellen Eierstocksgewebe," Arch. f. Gynak., vol. Ixxv., 1906.
8 Van Winiwarter, " Recherches sur 1'Ovogenese de 1'Organogenese de
1'Ovaire des Mammiferes," Arch, de Biol., vol. xvii., 1900.
CHANGES IN THE OVARY
119
changes which chiefly concern the chromatin of the nucleus
may be summarised as follows : —
I. Early changes : (a) Protobroque cells, Variety a. — The
FIG. 23. — Various stages in the development of the Graafian follicle of the
rabbit. (From Schafer.)
A, from young rabbit showing Pflliger's egg-tubes ; B, C, D, E, successive
later stages.
nuclei are granular in appearance, the chromatin is arranged
irregularly, and there is no reticulum. These are the original
120 THE PHYSIOLOGY OF REPRODUCTION
germinal epithelial nuclei. (b) Protobroque cells, Variety &.—
The cells belonging to Variety a divide, and give rise to more
cells of the same kind, as well as to protobroque cells of the b
variety. In the latter the nuclei are less granular, and contain
Early ovogenetic stage. Leptotenic stage.
a. 24. — Developing ova from ovary two days before birth.
Lane-Clayporj.)
(After
a certain number of fine chromatin filaments, (c) Deutobroque
cells. — The protobroque cells of the b variety likewise divide,
and give rise to more protobroque cells, similar to themselves,
and also to deutobroque cells. These latter are larger in size,
V,
Early. Synaptenic stage. Late.
FIG. 25. — Developing ova from ovary about one day before birth.
(After Lane-Claypon.)
and contain nuclei with the chromatin arranged in the form of
a reticulum.
II. Later changes : (a) Leptotenic stage.— Certain of the
deutobroque nuclei become gradually differentiated, the
chromatin during the leptotenic stage passing through a process
in which it breaks up into fine filaments ; these are distributed
CHANGES IN THE OVARY
over the nuclear region. (6) Synaptenic stage. — The filaments
become congregated together in the form of a lump, or dark
mass, heaped up at one side of the nuclear region, (c) Pachytenic
Pachytenic stage.
FIG. 26. — Developing ova from ovary one day after birth.
Lane-Clay pon.)
(After
stage. — The nuclear filaments again become unwound, and
spread themselves out over the whole nuclear region ; they are,
however, considerably coarser than in the earlier stages.
(d) Diplotenic stage. — The chromatin strands split along their
Diplotenic nucleus three
days after birth.
Dictyate nucleus seven
days after birth.
FIG. 27. — Developing ova. (After Lane-Claypon.)
whole length, and the two halves of each strand at first lie in
pairs near to one another, (e) Dictyate stage. — The split
strands pass away from one another, and the chromatin generally
becomes distributed once more throughout the nuclear region
in the form of a reticulum.
122 THE PHYSIOLOGY OF REPRODUCTION
The nucleus or germinal vesicle of the primordial ovum
thus produced then enters upon a long period of rest, the changes
involved in oogenesis having been completed.1
Some of the deutobroque cells, instead of passing through the
transformations above described, rest for a time and subse-
quently undergo retrogressive changes, becoming converted,
according to Miss Lane-Claypon, either into follicular epithelial
cells or into interstitial cells. " Every cell of the germinal
epithelium is probably a potential ovum, relatively very few
remaining in the protobroque state, although some may still be
seen at the periphery in ovaries of the eighteenth day [of gesta-
tion in the rabbit]. Incomparably the greater part pass into the
deutobroque state, preparatory, doubtless, to the formation of
ova. All cannot become ova, for the other forms of cell are
necessary for the maintenance of the ovarian functions ; pos-
sibly, therefore, only the most robust cells, and those which are
most conveniently situated for obtaining nourishment, undergo
the ovogenetic changes. This suggestion would seem to be
borne out by the fact that many more of the central cells, which
are nearer the food supply, undergo ovogenesis, than of the
peripheral ones. The rest of the cells which are not able, for
one cause or another, to undergo these changes, appear to
remain quiescent for a while, until finally they regress, and
pass into a condition of subserviency to the needs of those
which have become ova. Both follicle-cells and interstitial
cells are, however, still potential ova. They have passed
through the initial stages, and only need enlargement and
nuclear transformations in order to become ova should the
appropriate stimulus be given (as will be described below,
p. 160). This chance is not given to the follicle-cells. As
soon as the follicle begins to grow they multiply rapidly, and
1 For an account of the minute structure of the Mammalian egg, together
with a resume of the literature, see van der Stricht, " La Structure de 1'CEuf
des Mammifcres," Part I., Arch, de BioL, vol. xxi., 1904; Part II., Bull, de
I'Acad. Royale de Medecine de Belgique, Bruxelles, 1905; Part III., Bruxelles,
1909. For a general account of the egg and the phenomena of oogenesis in
the different groups of animals, both Vertebrate and Invertebrate, with a
complete bibliography, see Waldeyer, " Die Geschlechtszellen," in Herfcwig's
Handbuch der EntwicTclungslehre der Wirbelticre, vol. i., Jena, 1903 ; also Wilson,
The Cell in Development and Inheritance, 2nd Edition, New York, 1900.
CHANGES IN THE OVARY
123
probably provide, by their [partial] disintegration, the follicular
secretion upon which the ovum feeds and grows/' l
The description given above of the origin of the follicle
and interstitial cells applies especially to the rabbit. Miss Laner
Claypon has also investigated their developmental history in
the rat,2 and expresses belief that in this animal also they are
'«£v:*ju% ^
%«
K
*>
£
J*»v£»
'^lf"Wl4I?^
*u .^vm*^
&m*jSfiv£*
FIG. 28. — Ovary at birth, showing primordial follicles,
Williams' Obstetrics, Appleton & Co.)
x 300. (From
derived from the germinal epithelium by a similar process of
differentiation. Both follicular epithelial cells and interstitial
cells are stated to pass through identically the same stages, but
the latter are said to remain grouped together in the spaces
between the follicles instead of arranging themselves around the
diplotenic nuclei of the developing ova.
1 Lane-Claypon, loc. cit.
2 Lane-Claypon, " On Ovogenesis and the Formation of the Interstitial
Cells of the Ovary," Jour. Obstet. and Gyncec., vol. xi., 1907.
THE PHYSIOLOGY OF REPRODUCTION
Thus it appears that the ova, the follicular epithelial cells,
and most probably also the interstitial cells, are all derived from
the germinal epithelium by processes involving changes in the
nuclear chromatin ; but that, whereas these changes are similar
in the case of the follicle and interstitial cells, those undergone
by the developing ova are more extensive and show a greater
complexity.
The significance of the common origin of these different
ovarian elements will be more apparent when we consider the
views which are held regarding the further development and
the probable functional importance of these cells.
It should be mentioned, however, that Allen l and Sainmont,2
working on the organ ogenesis of the ovary in the rabbit and the
cat respectively, have come to the conclusion that the ovarian
interstitial cells have a connective tissue origin, but these in-
vestigators do not appear to have traced the successive stages of
cellular development with the same completeness as Miss Lane-
Claypon. Sainmont is of opinion that they have a trophic
function, a suggestion which was first made by Pfliiger.3
There would seem to be no doubt that the developing ova
in the immature ovary subsist and grow at the expense of the
surrounding tissue. Thus protoplasmic masses, formed by the
aggregation of very young ova, have been described by Balfour,4
who made the suggestion that one ovum may develop at the
cost of -the others. These aggregations of ova were noticed in
the ovary of the foetal rabbit at about the sixteenth day of
pregnancy. A day or two previously the ova were observed
to be separate. Miss Lane-Claypon, who confirms the observa-
tion, is of opinion that Balfour's suggestion was right, and that
the ova which disappear serve ultimately as food-stuff for the
1 Allen, " The Embryonic Development of the Ovary and Testis of the
Mammals," Amcr. Jour, of Anat., vol. iii., 1904. Allen describes the inter-
stitial cells in a three-months-old rabbit as being derived from certain cells in
the thecae internae of degenerate follicles. The cells are said to lose their
walls, become irregular in shape, and undergo a rapid process of amitotic
division, afier which they become transformed into typical interstitial cells.
2 Sainraont, ' Recherches relatives a 1'organogenese du Testicule et 1'Ovaire
chez le Chat " Arch, de Biol. vol. xxii., 1905.
3 Pfliiger, Ueber die Eicrstoclce der Sdugethitrc und des Menschen Leipzig.
1863.
4 Balfour, loc. cit.
CHANGES IN THE OVARY 125
one ovum whose condition happens to be the most vigorous.
' This cannibalism on the part of the young ovum is not sur-
prising, if the life of an ovum be considered. It is really but
the normal condition of the cell at all its stages of development ;
it grows and fattens at the expense of other cells. In the
young ovary, it is starting its first stage of growth and must
devour other cells ; later on, during the growth of the follicle,
it lives upon the follicle-cells, and later still, when, after fertilisa-
tion, the [term] ovum in its extended sense refers to the young
foetus, [this latter] lives on the material provided by the cells
of the maternal organism." 1
MATURATION AND OVULATION
The youngest and smallest Graafian follicles he near the
surface of the ovary, but pass inwards as they increase in size.
The large, mature follicles, however, come to lie just below the
surface from which they begin to protrude visibly at the ap-
proach of the breeding season. During the prooestrum one or
more follicles (the number varying in different animals, accord-
ing to the size of the litter) may generally be seen showing a
very considerable protrusion, while in some animals, such as the
sow, the appearance of the ovary at this time is not dissimilar
to a bunch of grapes.
A large Graafian follicle in a mature ovary contains the
following parts : Forming the outermost part of the wall and
in continuity with the ovarian stroma is the theca externa,
which is a layer of somewhat fibrous connective tissue. Within
this is the theca interna, which is less fibrous. The two thecse
are only slightly modified ovarian stroma. Within the theca
interna is the epithelial wall, which, in the very young follicles,
consists of a single layer of cells immediately surrounding the
ovum. These, as already mentioned, multiply rapidly (by
mitotic division) and give rise to a layer many cells deep, which,
as the follicle increases in size, becomes divided into two layers,
1 Lane-Claypon, " On Ovogenesis," &c., loc. cit. That one ovum may de-
velop at the expense of others is particularly well shown in Hydra, Tubularia,
and certain other Ccelenterates. The nuclei of the ingested ova continue
to be easily recognisable even during the early segmentation stages of the
developing egg.
126 THE PHYSIOLOGY OF REPRODUCTION
the membrana granulosa lining the follicle, and the discus
proligerus surrounding the ovum. The innermost cells of the
discus rest upon a thick, transparent, radially striated membrane
with a granular outer border. This is the zona radiata or zona
pellucida. The striated appearance is due to the presence of
fine canals. Within the zona, and immediately enclosing the
ovum, another very thin membrane can sometimes be made out.
This is the vitelline membrane. The membrana granulosa and
discus proligerus are united by one or more strands of follicular
epithelial cells. A viscid fluid, containing protein matter, collects
between them and becomes gradually
increased in quantity as the follicle
continues to grow.1
The liquor folliculi begins to form
in the developing rat's ovary at about
the ninth day of pregnancy.2 Miss
Lane-Claypon suggests that the kary-
olytic changes which occur in the
nuclei of the follicular epithelial cells
may have some connection with the
origin of the liquor. She states, how-
ever, that in the process of formation
of the liquor folliculi in the adult
ovary, the follicle cells appear simply
to disintegrate and dissolve without
showing the phenomena of karyolysis. On the other hand
Honore,3 who has investigated the subject in the case of the
rabbit, concludes that the liquor folliculi is secreted by the
follicle cells, without their undergoing destruction (or that, if this
occur, it is immaterial to the process of liquor formation), in the
same way as the urine is secreted by the epithelium of the renal
1 Occasionally a Graafian follicle may contain more than one ovum, but
this is abnormal. Such follicles have been described as occurring in the
rabbit's ovary by Honore (" Recherches sur 1'Ovarie du Lapin," Arch, de
Biol., vol. xvii. 1901), and in the dog's ovary by Smyth (" An Unusual Graafian
Follicle," Biol. Hull., vol. xiv., 1908). The latter writer states that one follicle
contained seven ova. He shows that the tendency to produce multiple ova may
be hereditary, and that it is apparently correlated with a high fertility.
2 Lane-Claypon, loc. cit.
3 Honore, "Recherches sur 1'Ovarie du Lapin," Arch, de Biol., vol. xvi.,
1900.
FIG. 29. — Young oocyte or
egg surrounded by a
single layer of follicular
epithelial cells. (From
van der Stricht.)
CHANGES IN THE OVARY
127
tubules. In support of this view Honore points out that there are
no indications of degeneration or destruction of the follicular
epithelial cells of the ripe follicles during oestrus, and moreover,
that these cells are retained in the follicle at the time of ovula-
tion, giving rise subsequently to the luteal cells of the corpus
luteum. It would appear possible, however, that the liquor
folliculi is formed partly by the secretory activity, and partly
•' '^3*£&slte&££3>if&£i
FIG. 30. — Young human Graafian follicle. The cavity contains the
liquor folliculi. (From Sellheim.)
by destruction of the follicle cells, just as, according to one
view, milk is derived from both the secretion and the disintegra-
tion of the cells of the mammary gland (see p. 560).
Heape l states that during the growth of the ovum nour-
ishment is supplied to it by the aid of the discus proligerus,
for fine protoplasmic processes may be seen passing from the
cells of this layer and projecting into radiating canals in the
zona which encloses the ovum, being in contact with the vitelline
membrane.
1 Heape, " The Development of the Mole," Quar. Jour. Micr. Science,
vol. xxvi., 1886.
128 THE PHYSIOLOGY OF REPRODUCTION
Immediately after copulation, and therefore during oestrus,
the cells of the discus proligerus (in the rabbit) 1 begin to with-
draw radially, and eventually remain attached to the zona
radiata by the extremely thin strands just referred to. At the
same time the ovum itself withdraws somewhat from the zona,
leaving a narrow circular space. These processes occupy some
FIG. 31. — Human ovum at termination of growth period. (After van
der Stricht.) Yolk granules, vacuoles, and fat drops are seen.
hours. About nine hours after copulation, when the supply of
nourishment has been entirely cut off, the two polar bodies are
formed, and the ovum becomes mature.
The essential facts about the maturation process were first
ascertained by van Beneden 2 in Ascaris, and were afterwards
1 Heape, " Ovulation and Degeneration of Ova in the Rabbit," Proc. Roy.
Soc., B., vol. Ixxvi., 1905.
2 Van Beneden, "Recherches sur la Maturation de 1'CEuf," Arch, dc BioL,
vol. iv., 1883.
CHANGES IN THE OVARY
129
studied more fully by Boveri.1 In recent years Montgomery 2
has elucidated the process still further by showing that prior
to the formation of the first polar body the chromatin filaments
FIG. 32. — Human ovum examined fresh in the liquor folliculi. (From
Waldeyer.) The ovum shows yolk granules in the centre surrounding
the nucleus (with its nucleolus) and a clearer peripheral portion. It
is enclosed by follicular epithelial cells.
1 Boveri, " Zellenstudien," Jenaische Zeitsch., vol. xxi., 1887.
2 Montgomery, " Some Observations and Considerations upon the Matura-
tion Phenomena of the Germ Cells," Biol. Bull., vol. vi., 1904. The references
to Montgomery's earlier memoirs dealing with the same subject are given in
this paper.
I
130 THE PHYSIOLOGY OF REPRODUCTION
or chromosomes of the cell nucleus conjugate together in pairs,
and that in all probability one member of each pair is a de-
scendant of a chromosome derived from the father, while the
other member is descended from a corresponding maternal
chromosome.1 The possible significance of this conjugation of
chromosomes is referred to on a later page (p. 196). In the
subsequent maturation division the chromosomes again separate.2
The changes involved in the formation of the first polar body
are in most respects similar to those of ordinary cell division.
The centrosome, which lies in the cytoplasm, divides, and the
two daughter centrosomes thus produced travel to opposite
sides of the nucleus. In the meantime; the latter forms a
spindle composed of the chromosomes, the nuclear membrane
having disappeared. Each centrosome becomes surrounded by
a system of rays, and in this way the attraction spheres are
formed. The chromosomes next arrange themselves equatorially
between the attraction spheres, each one having now split into
two parts. Half of these migrate towards each centrosome,
and the nucleus becomes divided. One of the daughter nuclei,
together with a thin investment of protoplasm, is extruded from
the ovum. This is the first polar body, which is therefore a
product of unequal cell division. Subsequently to extrusion
it sometimes divides into two. After the formation of the first
polar body, the ovum again divides in the same unequal fashion,
and the second polar body is formed and extruded. The polar
bodies undergo degeneration. Meanwhile the nucleus of the
ovum once more becomes surrounded by a membrane and enters
upon a resting stage.
The process of formation of the second polar body differs
from that of the first in that the chromosomes do not undergo
splitting. Consequently the nucleus of the mature ovum con-
1 The observations of this author, together with those of Sutton, McClung,
Wilson, &c., point to the conclusion that all the nuclei in the somatic cells
contain two parallel series of chromosomes (paternal and maternal).
2 In the redaction process each pair of fused chromosomes becomes
divided into a group of four bodies united by linin threads. These are the
tetrads or " vierergruppen." It follows that the number of tetrads in any
particular species is always one-half the number of somatic chromosomes.
Thus, if the somatic cells contain sixteen chromosomes, the number of tetrads
formed is eight, while, as shown in the text, the number of chromosomes in
the mature germ cells (after reduction) is also eight.
CHANGES IN THE OVARY 131
tains only half the original number of chromosomes. This
number varies in the different species, but is constant in each.1
In Man it is twenty-four, so that in the mature human ovum
there are only twelve chromosomes.2 As will be shown in the-
next chapter, the spermatozoa, or male germ cells, undergo a
similar process of maturation, the conjugating cells containing
only half the number of chromosomes characteristic of the species,
just as in the case of the conjugating ova. It has been sup-
posed, therefore, that the reduction in the number of chromo-
somes is a preparation on the part of the germ cells for their
subsequent union, and a means by which the number of
chromosomes is held constant in each species.
The discovery that the nuclei of the conjugating cells contain
only half the number of chromosomes possessed by the soma
or body cells was made originally by van Beneden. It has
since been extended to so many animals and plants that it
may probably be regarded as a general law of development.3
It is commonly believed that the chromatin material is
the substance which has the potentialities of development, and
which plays the principal part in perpetuating the hereditary
structure and qualities of the particular animal or plant, but
there is no real proof that this is the case (see p. 199 below).
The maturation phenomena may take place within the ovary
prior to the discharge of the egg, or they may be postponed
until after ovulation has occurred. In the rabbit, as has been
1 Van Winiwarter, however, states that in the rabbit the number varies
from thirty-six to eighty, but is generally about forty-two (Arch, de Biol.,
vol. xvi., 1900).
2 Duesberg, " Sur le Nombre chromosomes chez l'Homme," Anat. Anz.,
vol. xxviii., 1900.
3 For details of the process in various forms of life see Wilson, The
Cell, 2nd Edition, New York, 1900. See also Doncaster, "On the Matura-
tion of the Unfertilised Egg, &c., in the Tenthredinidas," Quar. Jour. Micr.
Science, vol. xlix., 1906 ; " Gametogenesis, &c.," Quar. Jour. Micr. Science,
vol. li., 1907. Doncaster shows that in the sawflies there are two types of
maturation process, in one of which there is no reduction. It is probable
that only the reduced eggs are capable of fertilisation. In other cases,
however, the ova are able to undergo parthenogenetic reproduction without
forming polar bodies. See Hewitt, " The Cytological Aspect of Partheno-
genesis in Insects," Manchester Memoirs, vol. lx., 1906; Doncaster, "Animal
Parthenogenesis," Science Progress, vol. iii. (July) 1908. These papers contain
further references.
132 THE PHYSIOLOGY OF REPRODUCTION
shown already,1 the polar bodies are formed while the ovum
is still in the ovary, but not until after the occurrence of
copulation.
In the case of the mouse, Sobotta 2 came to the conclusion that
the first polar spindle is suppressed, and that the second polar
body might be formed during the passage of the ovum down
the Fallopian tube. Gerlach 3 describes the second polar body
as being in some instances suppressed after the entry of the
spermatozoon in fertilisation, the second polar spindle degenerat-
ing within the egg. Kirkham,4 however, states that the matura-
tion of the mouse's ovum is in no way exceptional, the process
involving the formation of two polar bodies as in most other
animals. The first polar body is extruded in the ovary, while
the second is given off in the Fallopian tube immediately after
fertilisation by a spermatozoon.5 Rubaschkin 6 has shown that
the maturation processes in the guinea-pig are similar. In both
the guinea-pig and the mouse, ova which are retained in the
ovary, and also those which are discharged and fail to become
fertilised, undergo degeneration with the second polar spindle
within them.
The maturation phenomena in the bat (Vesperugo noctula)
have been investigated by van der Stricht, who has published a
1 Heape, loc. cit.
2 Sobotta, " Die Befruchtung und Furchung des Eies der Maus," Arch,
f. Mikr. Anat., vol. xlv., J895.
3 Gerlach, Ueber die Bildung der Richtungskorper bei Mus musculus,
Wiesbaden, 1906.
4 Kirkham, "The Maturation of the Mouse Egg," Biol. Bull., vol. xii.,
1907 ; and " The Maturation of the Egg of the White Mouse," Trans. Con-
necticut Acad. Arts and Sciences, vol. xiii., 1907.
5 Sobotta ("Die Bildung der Richtungskorper bei der Maus," Anat. Hefte,
vol. xxxv., 1907), in a further paper, expresses himself doubtful as to whether
two polar bodies are really discharged in all cases in the maturation process
of the mouse's ovum. His own observations lead him to conclude that two
polar bodies are discharged in not more than one-fifth of the total number
of maturations, only one polar body being formed in the great majority
of cases. Lams and Doorme (" Nouvelles Recherches sur la Maturation et la
Fecondation de 1'CEuf des Mammifcres," Arch, de Biol., vol. xxiii., 1907)
state that they found two polar bodies expelled in forty -four cases out of
forty-eight, the first being always smaller than the second.
6 Rubaschkin, " Ueber die Reifungs- und Befruchtungsprocesse des
Meerschweincheneies," Anat. Hefte, vol. xxix., 1905.
CHANGES IN THE OVARY 133
series of papers on the subject.1 This observer states that
there are always two polar bodies formed. The first is extruded
in the ovary. The second spindle is formed at about the ovulat-
ing stage, and the second polar body is discharged in the interior
of the Fallopian tube. The first body is formed in February
or March, or sometimes later, according to the temperature.2
It would seem that in the case of the mole the two polar
bodies are discharged while the ovum is still retained within
the ovary.3
In the pigeon it has been shown that the polar bodies are
given off while the ovum is passing down the glandular portion
of the oviduct and after the entrance of the spermatozoon.
The first polar spindle, however, is formed in the ovarian egg ;
but it is not definitely known at what stage fertilisation occurs,
excepting that it is previous to the time when the egg is clasped
by the oviducal funnel.
In the frog the polar bodies are extruded after ovulation has
taken place, but the egg is not set free until it has reached a
certain stage of maturation, which is preparatory to the dis-
charge of the first polar body. The nucleus undergoes a change,
and, in place of being large and watery, consists of a small mass
of chromatic substance lying in the protoplasm. An achromatic
spindle is developed, and the chromatin becomes arranged in
the form of granules at the equator of the spindle. The nuclear
membrane disappears with the large watery nucleus. The ova
in this condition pass into the oviducts.4
In certain Invertebrates (Nematodes, Annelids, and Gastero-
pods) it has been noticed that the occurrence of the maturation
1 Van der Stricht, " La Ponte ovarique," &c., Bull, de VAcad. Roy. de Mid.
de Belyiquc, 1901. Une Anomalie trh inte'ressante concernant le Developpcment
d'un CE'uf de Mammifere, Gand, 1904. "Les Mitoses de Maturation de 1'CEuf
de Chauve-Souris," Memoire pr<?scnte au VIIIe Congres de VAssoc. des Anato-
mistes, Nancy, 190fi.
2 Van der Stricht says (La Structure de VCEuf des Mammiferes, Bruxelles,
1909) that he has seen twenty-two ova at the stage of the second polar
spindle within the ovary and twenty-seven at the same stage outside of
the ovary, the dates varying in each case from the end of February to the
end of April.
3 Heape, " The Development of the-Mole," Quar. Jour. Micr. Science,vol. xxvi.
1886.
4 Morgan, The Development of the Frog's Egg, New York, 1897.
134 THE PHYSIOLOGY OF REPKODUCTION
phenomena depends upon the act of fertilisation. For example,
in the Japanese Palolo-worm, a marine Polychaet Annelid,
Izuka l has shown that the first polar body is discharged (after
certain preparatory changes) one hour after fertilisation by a
spermatozoon, and that the second polar body is extruded
fifteen or twenty minutes later. In other animals (e.g.
Amphioxus), one maturation process takes place before, the
other during the entrance of the spermatozoon.2
It would appear from these facts that the maturation pro-
cesses in many animals only take place as a result of a specific
stimulus which may be induced by the act of copulation, or may
be caused only by the entry of the spermatozoon into the proto-
plasm of the ovum. It would seem, on the other hand, that in
some animals maturation takes place independently of any
stimulus at such time as the follicle has attained to a sufficient
degree of ripeness or after it has discharged its ovum.3
It has already been shown incidentally that the processes of
maturation and ovulation are intimately associated, and that
the latter, like the former, is in many animals dependent for
its occurrence upon a definite physiological stimulus. The
Graafian follicle may rupture when the egg has reached a certain
degree of maturity, or it may require the additional stimulus of
sexual intercourse before ovulation can be induced.
In the rabbit ovulation takes place about ten hours after
coition.4 The ovum, which is entirely free from follicular
epithelial cells, is discharged into the infundibulum which at
this time closely invests the ovary. The discharged ovum is
incapable of assimilating nutriment unless it becomes fertilised,
1 Izuka, "Observations on the Japanese Palolo," Jour, of the Coll. of
Science, University of Tokyo, vol. xvii., 1903.
2 See Przibram, Embryogeny, English Translation, Cambridge, 1908.
3 The chemistry of the maturation process is discussed by Mathews
(" A Contribution to the Chemistry of Cell Division, Maturation and Fertilisa-
tion," Amer. Jour, of Phys., vol. xviii., 1907). This author describes the
maturation of the egg of Asterias as being inaugurated by the dissolution of
the nuclear membrane. If oxygen is withheld the mature egg soon dies.
It is believed that an " oxidase " escapes from the nucleus into the cytoplasm
on the rupture of the nucleus. The astral radiations disappear if oxygen is
withdrawn, but reappear if oxygen is readmitted. It is concluded that the
astral figures are the product of three substances : (1) centriole substance ; (2)
oxidase ; and (3) oxygen.
4 Heape, loc. cit.
CHANGES IN THE OVARY 135
and if fertilisation is not effected it undergoes degeneration.
Heape found that ovulation could not be induced by artificial
insemination, nor by any means other than sexual intercourse,
and moreover, that intercourse was a sufficient stimulus, everT~
when the progress of the spermatozoa from the vagina into the
uterus was artificially stopped, provided that there was no
interference with the vascular supply to the ovaries.
It is stated by Weil l that ovulation may take place inde-
pendently of coition in rabbits which have given birth to young
just previously, and Iwanoff,2 in confirmation of this statement,
records experiments in which pregnancy was induced in rabbits
by the artificial injection of seminal fluid shortly after par-
turition.
In the mouse,3 the rat,4 and the guinea-pig,5 ovulation
occurs spontaneously during " heat/' and generally, if not
invariably, during oestrus.
In the dog ovulation takes place independently of coition
after external bleeding has been going on for some days, or
when it is almost or quite over ; in other words, it occurs during
oestrus and not during the procestrum, or at any rate not during
the early stages of the prooestrum.6 It is probable that the
sow also ovulates during oestrus and not during the prooestrum,
since it is stated that sows are most successfully served on the
second or third day of " heat/' Coition, if it occurs earlier, is
frequently not followed by conception.7 From Hausmann's
description it would seem that ovulation does not take place
prior to coition, but this statement has not been confirmed.8
1 Weil, " Beitrage zur Kenntniss der Befruchtung und Entwickelung des
Kanincheneies," Wien Med. Jahrbuch, 1873.
2 Iwanoff, " La Fonction des Vesicles seminales et de la Glande pros-
tatique," Jour, de Phys. et de Path. Gen., vol. ii., 1900.
3 Sobotta, loc. cit.
4 G'afani, " La Fecondatipn et la Segmentation studied dans les (Eufs des
Rattes," Arch. Hal. de BioL, vol. ii., 1889.
5 Rubaschkin, loc. tit.
6 Marshall and Jolly, "Contributions to the Physiology of Mammalian
Reproduction: Part I. The (Estrous Cycle in the Dog," Phil. Trans., B.,
vol. cxcviii., 1905.
7 Wallace (R.), Farm Live Stock of Great Britain, 4th Edition, London,
1907.
8 Hausmann, Ueber die Zeugung und Entstehung des ivahren weiblichen Eies,
&c., Hanover, 1840.
136 THE PHYSIOLOGY OF REPRODUCTION
In the ferret ovulation occurs during oestrus, but postpone-
ment of coition may bring about the degeneration of the ripe
follicles, since they do not always discharge spontaneously.1
Artificial insemination, followed by pregnancy, has been
successfully performed on mares, donkeys, and cows.2 Conse-
quently it may be concluded that these animals ovulate inde-
pendently of coition. According to Ewart,3 ovulation in the
mare very often does not occur until near the end of the oestrous
period.
It has been shown also that the sheep ovulates spontaneously
at each of the earlier heat periods of the sexual season, but that
there are reasons for believing that during the later periods
the stimulating power at the disposal of the ewes may be so
reduced that without coition it is incapable of causing ovulation.
There is also evidence that when coition occurs at the beginning
of an oestrous period, it may provide a stimulus inducing ovula-
tion to take place a few hours earlier than it otherwise would ;
in other words, that if ovulation has not already occurred during
an oestrus, the stimulus set up by coition may hasten the rupture
of the follicle.4 Recently IwanofT has succeeded in inducing
pregnancy in sheep by artificial insemination. (See p. 183.)
There can be little doubt that in the great majority of
Mammals ovulation, as a general rule, occurs regularly during
oestrus. In certain bats, however, copulation is performed
during the autumn, whereas ovulation is postponed until the
following spring, the animals in the meantime hibernating,
while the spermatozoa are stored up in the uterus (see p. 177). 5
The ovary in the winter months (during the hibernating period)
is said to be in a state of quiescence, and the exact time for
1 Marshall, "The (Estrous Cycle in the Common Ferret," Quar. Jour.
Micr. Sci., vol. xlviii., 1904.
2 Heape, " The Artificial Insemination of Mammals," Proc. Hoy. Soc.,
vol. Ixi., 1897.
3 Ewart, " The Development of the Horse," MS.
4 Marshall, " The (Estrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans., B., vol. cxcvi., 1903.
5 Benecke, " Ueber Reifung und Befruchtung des Eies bei den Fleder-
mausen," Zool. Anz., vol. ii., 1879. Eimer, "Ueber die Fortpflanzung der
Fledermause," Zool. Anz., vol. ii., 1879. Van Beneden and Julin, " Observa-
tions sur la Maturation, la Ferondation, et la Segmentation de I'CEuf chez les
Cheiropteres," Arch, de BioL> vol. i., 1880.
CHANGES IN THE OVARY 137
maturation and ovulation depend upon the temperature of the
early months of the year, occurring generally in February or
March, but sometimes as late as April.1 Ovulation takes place
some days or even weeks after the formation of the first poIaF
body. It would appear, then, that in bats the follicles can
discharge spontaneously under the influence of appropriate
seasonal stimuli, and without even the occurrence of oestrus.2
There has been a considerable amount of controversy re-
garding the periods at which ovulation occurs in the Primates,
the question being discussed at some length in three papers by
Heape.3 This author has shown that ovulation and menstrua-
tion are not associated in monkeys (at any rate not necessarily),
and that whereas, in both monkeys and the human species,
menstruation may occur periodically all the year round, in
monkeys there is a limited season for conception and ovulation ;
while in civilised woman this period is not limited to any par-
ticular time of the year, although there is evidence that primi-
tively man agreed with the lower Primates in having a definite
sexual season (during which ovulation occurred). (See p. 71.)
Van Herwerden 4 has adduced further evidence which shows
that there is no apparent connection between ovulation and
menstruation, either in monkeys or in the aberrant lemur,
Tarsius spectrum. It would seem probable, however, in view
of Pocock's observations 5 upon the occurrence of a pronounced
post-menstrual oestrus in certain monkeys in the Zoological
Gardens, that ovulation may take place at this period (that is,
at the close of menstruation).
In the case of the human female there is still a great diver-
gence of opinion in regard to the usual time for the discharge
1 Van der Stricht, " L'Atresie ovulaire," &c., Verhand d. Anat. Gesell. in
Bonn, 1901. " Les Mitoses de Maturation," &c., Nancy, 1906.
2 In some Invertebrata which undergo cyclical changes it has been shown
that ovulation occurs only at certain intervals depending upon the general
condition of the organism. Thus in the females of certain Crustacea ovula-
tion regularly follows the moult and cannot precede it.— Science (New Series),
vol. xxv. (Feb. 1907).
3 Heape, Phil. Trans., JB., vol. clxxxv., 1894, and vol. clxxxviii., 1897.
Trans. Obstet. Soc., vol. xl., 1898.
4 Van Herwerden, " Bijdrage tot de Kennis van den Menstruellen Cyclus,"
Tijdschr. d. Ned. Dierk. Verccn, vol. x., 1906.
5 Pocock, "Notes upon Menstruation," &c., Proc. Zool. Soc., 1906.
138 THE PHYSIOLOGY OF REPRODUCTION
of the ova. Some authors express the belief that ovulation
occurs before menstruation, others that it takes place during
that process, and others again that it follows menstruation.
Hergesell l has lately adduced evidence which, in his opinion,
points to the conclusion that ovulation precedes menstruation,
but the occurrence of corpora lutea of uncertain age in the ovary
cannot be regarded as supplying definite proof. There are
reasons, on the other hand, for concluding that, primitively at
any rate, the most usual period for ovulation in the human
female was during a definite oestrus following a procestrum, as
in many of the lower Mammals ; for the period of most acute
sexual feeling is generally just after the close of the men-
strual period (see p. 69), while, according to Raciborsky, this
is also the commonest season for fertile coition.2 Moreover,
the facts narrated by Bryce and Teacher, in a recent memoir
on the early development and embedding of the human ovum,
render it extremely probable that the ovum described had
been discharged shortly after the cessation of the last men-
struation.3
With regard to the question as to whether any special
stimulus is necessary to induce ovulation in women, Oliver 4 is
of opinion that whereas it sometimes may occur spontaneously,
it is more than probable that it " may be and often is accelerated
by coitus/' since at this time there is " an increased determina-
tion of blood to the whole genital tract." 5
1 Hergesell, "Das zeitliche Verhalten der Ovulation zur Menstruation."
Inaug. Diss., Leipzig, 1905.
2 Raciborsky, Traite de Menstruation, Paris.
3 Bryce and Teacher, Contribution to the Study of the Early Development
and Embedding of the Human Ovum, Glasgow, 1908-
4 Oliver, "A Study of Fertilisation with Reference to the Occurrence of
Ectopic Pregnancy," Edin. Med. Jour., vol. liv., 1902.
5 Pregnancy, and therefore ovulation, have been known to take place
before the onset of menstruation. Pregnancy may also occur during amenor-
rhoea (e.g. at the commencement of the menopause) and during the lactation
period, when menstruation is often in abeyance. Again, it is stated that
ovulation has been noted during infancy, before any of the other indications
of puberty have been observed (Webster, " The Biological Basis of Menstrua-
tion," Montreal Medical Journal, April 1897). Further, it will be shown below
(p. 348) that the ovaries can maintain their normal functions after the
removal of the uterus. It would seem, therefore, that ovulation may occur
spontaneously in women, and is not necessarily connected with either men-
CHANGES IN THE OVARY 139
This suggestion receives some support from an experiment
by Clark,1 who caused the rupture of a Graafian follicle artificially
in a freshly removed ovary by injecting carmine gelatine into_
the vessels and so raising the ovarian blood pressure.
The causes which determine the rupture of the Graafian
follicle are also discussed by Heape,2 who is of opinion that
this is brought about in the rabbit by the stimulation of erectile
tissue, and not simply as the result of internal pressure arising
from increased vascularity or a greater quantity of liquor folliculi.3
In this animal the process must be due to a nervous reflex, in-
duced by the act of copulation. As has been shown above, in
those animals in which the ova are discharged spontaneously,
this usually occurs during oestrus, and not during the prooestrum
when the congestion of the generative tract is at its height.
Harper's experiments 4 on the fertilisation of the pigeon's egg
elucidate the question somewhat further. This author writes as
follows : " When a pair [of pigeons] ready for mating is put
together, egg-laying ordinarily ensues at the end of a rather
definite period, at the least eight days. The female functions
are held in abeyance till the proper stimulus is received from a
mate.5 The maturing of the egg is so exclusively a female
function that it seems odd at first thought that an apparent
exception should occur to the rule. Of course, we know that
struation, oestrus, or coitus. On the other hand, there is evidence that
ovulation is intimately associated with the occurrence of the sexual orgasm
in certain instances. Thus Galabin records a case of a woman who married
under the age of twenty, and lived in married life with two husbands in
succession, and who, when she had passed the age of forty, experienced the
sexual orgasm in coitus for the first time, and from that day dated her first
and only pregnancy (Manual of Midwifery, Gth Edition, London, 1904). The
orgasm (which is characterised by the erection of the clitoris, accompanied by
certain sensations) is not necessary for conception, for pregnancy often occurs
in women who are " impotent."
1 Clark, " The Origin, Development, and Degeneration of the Blood-Vessels
of the Human Ovary, " Jo/ins Hopkins Hospital Reports, vol. ix., 1900.
2 Heape, " Ovulation," &c., Proc. Roy. Soc., £., vol. Ixxvi., 1905.
3 It has been suggested that the follicle may rupture as a result of the
breaking down of the blood-vessels in its wall, and the consequently increased
pressure due to the bleeding into the cavity. See Heape.
4 Harper, "The Fertilisation and Early Development of the Pigeon's
Egg," Amer. Jour, of Anat., vol. iii., 1904.
5 In the common fowl, and probably in most other birds, ovulation takes
place independently of the male.
140 THE PHYSIOLOGY OF REPRODUCTION
the final maturation of the egg, or the giving off of the polar
bodies, awaits in most animals the act of fertilisation. But
here the effect is produced upon the egg by the entrance of
sperms. How mating and the act of copulation [which is re-
peated at frequent intervals every day at this time] could in-
fluence the ripening of the egg in the ovary is another problem.
In this connection the curious fact must be mentioned that
two female pigeons placed in confinement may both take to
laying eggs. The function of ovulation is in a state of tension,
so to speak, that requires only a slight stimulus, ' mental '
apparently in this case, to set the mechanism to working. At
any rate, it is impossible to regard the presence of sperm in the
oviduct as an essential element of the stimulus to ovulation,
although it may have an important influence in the normal
case. Our attention is directed to the various and complex
instincts of the male which come under the head of courtship,
both before and after mating is effected, as furnishing a part of
the stimulus to the female reproductive organs/' Harper pro-
ceeds to describe a curious habit which is common among
pigeons before copulating. The male bird regurgitates some
secretion in its throat, and this is taken up by the bill of the
female in much the same manner as the young take their food.
"It is easy to see that here may be one of the sources of in-
direct stimulation to the female reproductive organs."
Spallanzani 1 found that whereas the female fire-bellied toad
could lay its eggs in the absence of the male, the female fetid
toad, if isolated, retained its eggs in the ovaries. The common
frog is capable of spontaneous oviposition, at least in some
cases.2
The exact nature of the mechanism by means of which the
discharged ova in the human female are made to pass into the
aperture of the oviduct is not certainly known. Rouget 3 be-
lieved that the fimbriated end of the Fallopian tube erected
and partially enclosed the ovary. Kehrer 4 suggested that the
1 Spallanzani, Dissertations, English Translation, London, 1784.
2 Morgan, The Development of the Frog's Egg, New York, 1897.
3 Rouget, " Recherches sur les Organes Erectiles de la Femme," Jour, de
la Phys., vol. i., 1858.
4 Kehrer, "Die Zusammenziehungen des Weiblichen Genitalcanals,"
Beitrdge zur Vergleich. und Exper. GeburtsJcunde, 1864.
CHANGES IN THE OVARY 141
ovum was shot into the open fimbrise in the act of ejaculation.
The motion of the cilia, which line the fimbriated end as well as
the interior of the tube, no doubt serve to set up a current
which assists in directing the ova. Gerhardt,1 who has paid
some attention to the question, concludes that in Man and many
other Primates a number of factors co-operate to secure the
entry of the discharged ovum into the tube. These factors
include the erectibility of the fimbrise, the muscular movements
of the same, the ciliary currents on the fimbrise and tube, and
the configuration of the ovarian surface. In other orders of
Mammals the process is brought about in various ways. In
Monotremes, Marsupials, and Cetaceans the entrance to the tube
is relatively large as compared with the size of the ovary. In
certain other animals a portion of the peritoneum is used as a
common envelope for the ovary and the end of the tube. Thus
in the dog and ferret the ovary is enclosed in a sac communicating
with the cavity of the tube, so that the discharged ova can
scarcely fail to effect an entrance into the uterus. There can
be little doubt, however, that in the majority of animals ciliary
movement plays an important part in directing the course of
the expelled ova.
Nussbaum 2 has described the eggs of the frog as being
carried into the mouths of the oviducts by the motion of the
cilia of the ccelomic epithelium. These cilia are said to drive
in a forward direction any small bodies lying free in the ccelom.
Harper 3 states that in the pigeon the egg is clasped by the
oviduct, which at this time displays active peristaltic contrac-
tions, as if in the act of swallowing the egg.
There is evidence, however, that ova which are discharged
from one ovary do not always pass into the oviduct on
the corresponding side. For example, instances have been
known of animals with a bicornuate uterus becoming pregnant
in the uterine horn on the side opposite to that on which the
ovary had discharged (as indicated by the presence of a newly
1 Gerhardt, " Studien iiber den Geschlechtsapparat der Weiblichen Sauge-
thiere : I. Die Ueberleitung des Eies in die Tuben," Jcnaische Zeitschr.,
vol. xxxix., 1905.
2 Nussbaum, "Zur Mechanik der Eiablage bei Eana fusca," Arch. f. Mikr.
Anat., vol. xlvi., 1895.
3 Harper, loc. cit.
142 THE PHYSIOLOGY OF REPRODUCTION
formed corpus luteum). Moreover, it has been recorded that
animals from which one ovary had been removed have become
pregnant in both horns of the uterus, an observation which
clearly shows that the ova which are discharged from one ovary
may travel across the peritoneal cavity and enter into the
Fallopian tube on the other side of the body.
In certain abnormal cases the ovum escapes altogether into
the peritoneal cavity, and never finds its way into either ovi-
duct. If the ovum becomes fertilised, as sometimes happens,
the condition known as ectopic or extra-uterine gestation may
result ; that is to say, the embryo which is formed may become
attached to some part of the wall of the body cavity and there
undergo development. Ectopic or extra-uterine pregnancy has
been known to occur in the domestic animals as well as in the
human subject.1 Thus Gofton 2 has recently described a case
of a cat which was pregnant with six kittens, one in the normal
position in the uterus, and the other five in the abdominal
cavity. The fcetal envelopes of the abdominal embryos were
attached by a sort of placenta to the parietal peritoneum and
to the omentum, and one had also an extensive attachment
to the fundus of the stomach. All the embryos were well
developed and apparently normal. Moreover, Dr. Blair Bell
has informed me of a case of primary abdominal pregnancy in a
rabbit owned by him. There were four well-developed foetuses.
THE FORMATION OF THE CORPUS LUTEUM
After the discharge of the ovum from the ovary the ruptured
Graafian follicle undergoes a series of changes which result in
the formation of the structure known as the corpus luteum.
The fully formed corpus luteum consists of large cells con-
taining a yellow pigment, the luteal cells, separated from one
another by an anastomosis of connective tissue which is seen
to branch inwards from the surrounding ovarian stroma, and
1 See the text-books on Midwifery, and for further details, The Journal of
Obstetrics and Gynaecology, vol. x., December 1906, which number is entirely
devoted to the subject of extra-uterine pregnancy. Ovarian pregnancies, in
which the spermatozoa have entered newly ruptured follicles, are also known.
2 Gofton, " Ectopic Gestation in a Cat," Royal Dick Coll. Mag., vol.
i., 1906.
CHANGES IN THE OVARY 143
to form a central plug in which there are no luteal cells. This
connective tissue contains numerous blood-vessels, so that the
fully developed corpus luteum is a highly vascular structure.
Three hypotheses have been put forward regarding the
manner of formation of the corpus luteum. That of Paterson,1
who supposed it to be derived from the blood coagulum left in
the cavity of the Graafian follicle after its discharge, gained few
or no adherents. The other two theories, those of von Baer 2
and Bischoff,3 on the other hand, have each received consider-
able support.
Von Baer regarded the corpus luteum as an entirely con-
nective tissue structure, in the origin of which the follicular
epithelium had no share ; while BischofE concluded that the
luteal cells were formed by the hypertrophy of the epithelial
cells of the undischarged Graafian follicle. Among the principal
supporters of Von Baer's view appear the names of Leuckart,
His, Kolliker, Slavjansky, Gegenbaur, Benckiser, Schottlander,
and Minot. Those who have adopted the alternative theory of
Bischoff include Pfliiger, Waldeyer, Gill and Exner, Beigel and
Schulin.4
To Sobotta 5 belongs the credit of being the first to deal
systematically with the question, and, with the publication of
his papers on the corpus luteum in the mouse, the controversy
entered upon a new phase. In Sobotta's investigation the
material employed was collected upon a definite plan, the
animals being killed at known intervals after coition, in re-
ference to the occurrence of which the period of ovulation had
been previously determined. In this way there was obtained
a large series of corpora lutea representing successive stages of
development. The investigation resulted in confirming BischofPs
1 Paterson, " Observations on Corpora Lutea," Edinburgh Med. and Surg.
Jour., 1840.
3 Von Baer, De Ovi Mammalium et Hominis Genesi Epistola, Lipsise,
1827.
3 Bischoff, Entwickelungsgeschichte des Kanincheneies, Braunschweig, 1842.
4 For an account of the older literature of the subject see Sobotta, " Uber
die Entstehung des Corpus Luteum der Saugethiere," Merkel and Bonnet's
Ergcbnisse dcr Anat. u. Entwick., vol. viii., 1899.
5 Sobotta, " liber die Bildung des Corpus Luteum bei der Maus," Anat.
An-., vol. x., 1895 ; and Arch. f. Mikr. Anat., vol. xlvii., 1896.
144 THE PHYSIOLOGY OF REPRODUCTION
view that the luteal cells are the much hypertrophied epithelial
cells of the undischarged follicle, the connective tissue network
being derived from the inner layer of the theca. Sobotta de-
scribes the outer theca as taking no share in the ingrowth,
while the theca interna is stated to become entirely spent in
the formation of the inter-epithelial anastomosis. The hyper-
trophy of the epithelial cells is said to be of the nature of a
simple enlargement, unaccompanied by division.
Sobotta 's conclusions in regard to the development of the
corpus luteum in the mouse were subsequently confirmed by
a
FIG. 33.— Recently ruptured follicle of mouse. (From Sobotta.)
/<?, follicular epithelium or meuubrana granulosa (somewhat hyper-
trophied) ; th, theca interna; a, ingrowth from same.
him in a further investigation carried out on similar lines on the
corpus luteum in the rabbit.1 Moreover, Stratz 2 published de-
scriptions of certain stages of corpus luteum formation in Tarsius,
Tupaia, and Sorex, and these agree in essential particulars with
those given by Sobotta ; while Honore,3 also working on the
rabbit, differed only in concluding that the inter-epithelial
network is derived in part from the theca externa, and not
exclusively from the theca interna, and that the latter is
not entirely exhausted by the ingrowth, some part of it still
1 Sobotta, " tiber die Bildung des Corpus Luteum beim Kaninchen."
Anat. Hefte, vol. viii., 1897.
2 Stratz, Der Geschlechtsrcife Sauyethiereierstock, Haag, 1898.
3 Honore", "Recherches sur 1'Ovaire du Lapin," Arch, de Biol., vol. xvi.,
1900.
CHANGES IN THE OVARY
145
remaining to form a layer within the outer theca in the fully
formed corpus luteum.
On the other hand, several investigators have expressed
doubts regarding Sobotta's conclusions, and some have adoptedr~
the theory originally formulated by von Baer that the luteal
cells arise from the connective tissue sheath of the follicle, the
follicular epithelium being either entirely discharged along with
the ovum or else being partially discharged and partially de-
generating in situ. Amongst those who have adopted this
view are Nagel,1 who investigated the human corpus luteum ;
FIG. 34. — Early stage in formation of corpus luteum of mouse. (From
Sobotta.)
I, developing luteal cells ; e, germinal epithelium.
Clark,2 who contributed an account of the formation of
the corpus luteum in the sow and in the human subject ;
Doering,3 who also worked upon the sow, and claimed to
have confirmed Clark's account ; and Biihler,4 Wendeler,5
1 Nagel, " Die Weiblichen Geschlechtsorgane," Bardeleben's Handbuchder
Anatomic des Menschen, vol. vii., Jena, 1896. " tJber neuere Arbeiten auf clem
Gebiete der Anatomic der weiblichen Geschlechtsorgane," Merkel and
Bonnet's Ergebnisse d. Anat. u. Entwick, vol. viii., 1899.
2 Clark, " Ursprung, Wachstum, und Ende des Corpus Luteum," Arch. f.
Anat. u. Phys., Anat. Abth., 1898 ; Johns Hopkins Hospital Reports, vol. vii., 1899.
3 Doering, " Beitrag zur Streitfrage uber die Bildung des Corpus Luteum,"
Anat. Anz., vol. xvi., 1899.
4 Buhler, " EntwickelungsstadienMenschlichen Corpora Lutea," Verhand.
d. Anat. Gesell., in Pavia, 1900.
5 Wendeler, Martin's Die Krankheiten der Eierstocke und Nebeneierstocke.
K
146 THE PHYSIOLOGY OF REPRODUCTION
and Stockel,1 who have examined and described developing
human corpora lutea. Moreover, His,2 Kolliker,3 and Paladino 4
have reiterated their adherence to von Baer's hypothesis since
the publication of Sobotta's work.
It is remarkable, however, that none of the supporters of
this hypothesis appear to have examined the growing corpus
luteum in all its stages of development, while in the case of
several of the accounts it is not clear whether the structures
described were not in reality atretic follicles — that is to say,
FIG. 35. — Late stage in formation of corpus luteum of mouse. (From
Sobotta.) Thecal ingrowths are numerous. The cavity of the follicle
is not yet filled in.
follicles which had undergone degenerative changes without ever
being discharged. Thus, the words used in a description given
by Clark seem to indicate that this author was dealing with the
degenerative epithelial cells of an atretic follicle. It seems not
impossible also that the young human " corpus luteum " de-
scribed by Doering was a degenerate follicle ; while Kolliker 's
opinion that the corpus luteum is an entirely connective tissue
structure appears to have been founded on the assumption that
1 Stockel," Ueber die Cystiche Degeneration der Ovarien bei Blasenmole,"
Sep. Abdruck aus der Festschrift fiir Fritsch.
2 His, Discussion, Verhand. d. Anat. Gesell., in Tubingen, 1899.
3 Kolliker, " Ueber Corpora Lutea Atretica bei Saugethieren," Verhand.
d. Anat. OeselL, in Kiel, 1898.
4 Paladino, "Per la Dibuttata Questione sulla Esenza del Corpo Luteo,"
Anat. Anz., vol. xviii., 1900.
CHANGES IN THE OVARY
147
the changes exhibited by discharged follicles and retrogressive
undischarged follicles are identical in character. It is to be
noted further that in the investigations of all those writers who^
have upheld the connective tissue hypothesis, the ages of the
developing corpora lutea were unknown, the material having
been collected in no case by Sobotta's method of killing the
animals at successive intervals after coition.
In 190.1, after the publication of the papers referred to above,
FIG. 36. — Corpus luteum of mouse fully formed. (From Sobotta.) Theluteal
tissue is vascularised and the central cavity filled in with connective
tissue.
the present writer issued a preliminary account 1 of an experi-
mental inquiry upon the formation of the corpus luteum in the
sheep. In this inquiry the animals were killed at successive
intervals after coition, or (in cases where coition did not or was
not known to occur) after oestrus was observed. The result of
this investigation was to confirm BischofFs hypothesis in all
1 Marshall, "Preliminary Communication on the (Estrous Cycle and the
Formation of the Corpus Luteum in the Sheep," Proc. Roy. Soc., vol. Ixviii.,
1901. The full paper was afterwards published in the Phil. Trans., B.,
vol. cxcvi., 1903.
148 THE PHYSIOLOGY OF REPRODUCTION
essential particulars. The sheep, however, was found to present
some differences from the mouse (as investigated by Sobotta)
in regard to the origin of the connective tissue network of the
corpus luteum, this being discovered to originate partly from
the theca externa, and not merely from the theca interna. It
was found also that the cells of the follicular epithelium con-
tinued to undergo mitotic division after the rupture of the
follicle, but not with the same frequency as previously. The
theca interna was stated to become entirely spent in the growth
of the connective tissue network. Four days after oestrus the
discharged follicle was found to. have acquired all the char-
acteristics of the fully developed corpus luteum, the luteal cells,
as seen in section, being at least six times as large as the original
epithelial cells.
In the same year as the publication of the paper referred to
above, on the sheep's corpus luteum, van der Stricht l gave an
account of the discharged follicle in bats belonging to the genera
Vesperugo, Vespertilio, and Placotus. This was also confirmatory
of the conclusion that the follicle cells hypertrophy and give rise
to luteal cells, but mitotic division among these cells was also seen
to occur. Van der Stricht calls attention to the appearance of
fatty particles at a very early stage in the history of the luteal
cells. A point of greater importance is that van der Stricht
found that, whereas the majority of the luteal cells are derived
from the follicular epithelium, a certain relatively small pro-
portion of them are developed out of interstitial cells in the
inner theca of the connective tissue sheath. This observation
lends additional interest to Miss Lane-Claypon's statement that
the follicle and interstitial cells have an identical origin, since
both are derived from the germinal epithelium, and pass through
a similar series of changes.2
The structure of the ovary, and the cyclical changes which it
1 Van der Stricht, " La Rupture du Follicule Ovarique et 1'Histogenese du
Corps Jaune," C. R. deVAssoc. des Anatomistes, 3rd Session, Lyon, 1901. " La
Ponte Ovarique," &c., Bull, de VAcad. Roy. de Mtdecine Bdgiquc, 1901.
'2 Marshall, "The Development of the Corpus Luteum : a Review," Quar.
Jour. Micr. Science, vol. xlix., 1905. Miss Lane-Claypon's discovery that the
follicular epithelial and interstitial cells are probably equipotential may per-
haps help to elucidate some of the discrepancies between the accounts by
various authors of the formation of the corpus luteum.
CHANGES IN THE OVARY 149
undergoes in the case of the " marsupial cat " (Dasyurus
viverrinus), have been investigated by Sandes,1 who shows that
the mode of formation of the corpus luteum in Marsupials is
essentially similar to what it is in the Eutheria. The thecn
interna folliculi is shown to be rudimentary in Dasyurus, a
circumstance which rendered it especially easy to follow the
subsequent changes undergone by this layer. Sandes describes
the follicular epithelium as undergoing so great an hypertrophy
prior to the thecal ingrowth as sometimes almost to fill the
cavity of the discharged follicle, so that there could be no possi-
bility of confusing the epithelial with the connective tissue cells.2
The formation of the corpus luteum in the rabbit has been
further studied by Cohn,3 while the same process in the marmot
has formed the subject of an investigation by Volker.4 Both
authors agree in supporting BischofL Volker finds that the
theca externa takes a share in the connective tissue ingrowth,
while the theca interna does not become exhausted in the
process.
Jankowski,5 however, has arrived at totally different conclu-
sions, and adopts the view that the luteal cells are modified
connective tissue cells. The material employed in this research
appears to have consisted of a miscellaneous collection of sows'
and guinea-pigs' ovaries obtained without any attempt at syste-
1 Sandes, " The Corpus Luteum of Dasyurus Viverrinus," Proc. Linnean
Soc., New South Wales, vol. xxviii., 1903.
2 Through the kindness of Professor J. P. Hill I have been permitted to
examine sections in his possession of the corpus luteum of the Monotreme
Ornithorhynchus paradoxus. These sections show much hypertrophied and
apparently fully developed luteal cells, but no trace of any ingrowth from the
connective tissue wall of the corpus luteum.
3 Cohn, " Zur Histologie und Histogenesis des Corpus Luteum und des
Interstitiellen Ovarialgewebes," Arch. f. Mikr. Anat, vol. Ixii., 1903.
4 Volker, " Uber die Histogenese Corporis Lutei bei den Ziesel (Spermo-
philus citillus}" Bull, fnternat. Acad. Sci. (Medicine), Prague, 1904.
5 Jankowski, " Beitrag zur Entstehung des Corpus Luteum der Sauge-
thiere," Arch. f. Mikr. Anat., vol. xliv., 1904. Williams (Obstetrics, New
York, 1904) takes up the same position as Jankowski, partly on the ground
that " the membrana granulosa presents extensive degenerative changes, and
is usually cast off in great part at the time of rupture," and partly because
certain cells of the theca interna come to resemble luteal cells prior to ovula-
tion. The former statement is far from proved, and the latter cannot be
regarded as conclusive (see text). Cf. also Seitz, " Die Follikelatresie," Arch,
f. Oyndk., vol. Ixxvii., 1906.
150 THE PHYSIOLOGY OF REPRODUCTION
matic investigation, so that the ages of the corpora lutea were
unknown. Jankowski bases his opinion largely on the appear-
ance of cells resembling luteal cells in the theca interim of
the undischarged follicle. It would seem possible that these
were interstitial cells, and so probably potentially equivalent
to follicle cells (as supposed on independent grounds by van
der Stricht and Miss Lane-Claypon).
Sobotta,1 however, and also Loeb,2 have subsequently in-
vestigated the formation of the corpus luteum in the guinea-pig,
and find that it is substantially the same as in the mouse, the
rabbit, and the sheep.
The results of those investigators who agree in adopting
Bischoff s theory of the mode of formation of the corpus luteum
may be summarised as follows : — The luteal cells represent the
epithelial cells of the undischarged Graafian follicle. These,
after rupture, undergo a great hypertrophy, which may be
accompanied in the earlier stages by mitotic division, but only
to a relatively slight extent (Ovis, Vesperugo, &c.). Meanwhile
the thickness of the wall of the discharged follicle is further
increased by an ingrowth of connective tissue, which eventually
forms an anastomosis of cells, generally fusiform in shape, be-
tween the hypertrophying follicular epithelial cells. This con-
nective tissue ingrowth is either derived from the theca interna
alone (Mus, Cavia, Tarsius, Tupaia, Sorex, Dasyurus, Vesperugo,
&c.), or it may arise from both the theca interna and the theca
externa (Lepus, Ovis, Spermophilus). The theca interna may
become entirely spent in this process (Mus, Cavia, Tarsius,
Tupaia, Sorex, Ovis, Dasyurus), or certain strands of this layer
may still remain and line the outside edge of the follicle after
it has become transformed into a fully developed corpus luteum
(Lepus, Spermophilus, Vesperugo). In some animals the inter-
stitial cells of the theca interna may develop into luteal cells
in just the same manner as the follicular epithelial cells
(Vesperugo, &c.). The cavity of the discharged follicle becomes
filled in eventually by the further ingrowth of connective tissue,
which forms a central plug.
1 Sobotta, " Uber die Bildung des Corpus Luteum beim Meerschweinchen,"
Anat. Hefte, vol. xxxii., 1906.
2 Loeb (L.), "Uber die Entwicklung des Corpus Luteum beim Meer-
schweinchen," Anat. Anz., vol. xxviii., 1906.
CHANGES IN THE OVARY 151
The changes undergone by the discharged follicle have also
been studied in certain of the lower Vertebrates. Giacomini,1
who has investigated the subject in birds, amphibians, and, -
more particularly, Elasmobranch fishes, describes an hyper^
trophy of the follicular epithelium consequent upon ovulation.
The discharged follicle of Myliobatis is described and figured as
a glandular body in which the enlarged epithelium is pene-
trated by an extensive ingrowth of connective tissue and blood-
vessels. Wallace 2 gives a somewhat similar account of the
spent follicles in the fishes Zoarces and Spinax. In the latter
especially there is a pronounced hypertrophic enlargement of
the follicle cells, associated with thecal ingrowths arrayed in
a radial manner. Lucien 3 has described corpora lutea in the
reptiles Anguis and Seps, in which there is a simple hypertrophy
of the follicular epithelium unaccompanied by mitotic division.
Similar structures in reptiles have also been observed by
Mingazzini,4 who believes them to be identical with mammalian
corpora lutea. On the other hand Biihler,5 who investigated
the ovaries of Cyclostomes and certain Teleosteans, was
unable to find any hypertrophy of the wall of the spent follicle,
and Cunningham,6 also writing on Teleosteans, arrived at the
same result as Biihler. However, it is evident that the epithelial
theory of the origin of the corpus luteum receives confirmation
from those members of the lower Vertebrata in which there is a
follicular enlargement following ovulation.
The mammalian corpus luteum may contain a central clot
composed of blood derived from the vessels of the follicular wall
which gave way at the time of ovulation. In this case the
blood-clot becomes gradually absorbed along with the remainder
1 Giacomini, "Contribute all 'Istologia dell' Ovario dei Selaci," Ricerca
Lab. di Anat. Normale delta Roy. Univ. di Roma, vol. v., 1896.
a Wallace (W.), "Observations on Ovarian Ova, &c.," Quar. Jour. Micr.
Science, vol. xlvii., 1903.
3 Lucien, "Note preliminaire sur les premieres Phases de la Formation
des Corps Jaune chez certains Reptiles," C. R. de Soc. dc Biol., vol. lv., 1903.
4 Mingazzini, " Corpi Lutei verie falsi da Rettili," Ricerca Lab. di Anat.
Normale dclla Roy. Univ. di Roma, vol. iii., 1893.
5 Biihler, " Riickbildung der Eifollikel bei Wirbelthieren," Morph. Jahr.,
vol. xxx., 1902.
8 Cunningham (J. T.), " On the Histology of the Ovary and of the Ovarian
Ova in certain Marine Fishes," Quar. Jour. Micr. Science, vol. xl., 1897.
152 THE PHYSIOLOGY OF REPRODUCTION
of the liquor folliculi. On the other hand, there may be practically
no haemorrhage, or the discharged blood may be expelled to the
exterior of the ovary (with the greater part of the liquor), remain-
ing as a small clot upon the surface.1 It would seem probable
that the vessels burst as an effect of the released tension conse-
quent upon the rupture of the follicle ; but, as already mentioned,
it has been suggested that possibly the latter process may itself
occur as the result of the pouring out of blood into the
cavity. During the early stages of formation of the sheep's
corpus luteum leucocytes of the polymorph variety have been
observed in great abundance, but in the later stages they
disappear, some of them undergoing degeneration. These
leucocytes are not extravasated, but wander inwards with the
growing strands of connective tissue.2 Their occurrence should
probably be associated with the necessity to dispose of the
blood-clot when such is present.
The ingrowth of connective tissue commences a very short
time after ovulation, and in the sheep may be seen very dis-
tinctly as early as in the seven-hour stage of development.
Blood-vessels are carried inwards with the connective tissue,
and these undergo multiplication, so that the corpus luteum is
a highly vascular structure.
If the discharged ovum fails to become fertilised the corpus
goes on growing for a short time and then degenerates, so that,
in the case of the human female, two months after ovulation
it is reduced to the condition of an insignificant cicatrix. In
the smaller animals it disappears after a considerably shorter
time. If, on the other hand, conception succeeds ovulation, the
corpus luteum continues to increase in size until almost the
middle of pregnancy, and in the human female attains to a
diameter of nearly an inch in length.
The large size of the completely developed corpus luteum
is the more remarkable in that it results to so large an extent
from the simple hypertrophy of certain of its constituent cells.
1 It is sometimes stated that the haemoglobin of the blood-clot is trans-
formed into the yellow pigment (known as lut-ein) which gives the luteal cells
their characteristic colour ; but this is obviously incorrect, since there may
be no blood-clot in the follicle, whereas the luteal cells always contain
lutein.
2 Marshall, Phil. Trans., loc. cit.
CHANGES IN THE OVARY
153
The wonderful property which these cells possess of enlarging
within a very short time of ovulation is seemingly without a
parallel in the physiology of the Vertebrata, and it becomes^
additionally interesting in view of the almost certain fact that
the cells, from which the luteal cells develop, are derived, like
the ova, from the original germinal epithelium.
During the later part of pregnancy the corpus luteum becomes
FIG. 37- — Section through old corpus luteum. (From Sellheim.)
C, connective tissue ; L, luteal tissue.
reduced in size, the luteal cells degenerating, losing their yellow
colour, and eventually (at least in some cases) appearing to
become transformed into cells resembling, if not identical with,
the ovarian interstitial cells referred to above (see p. 148).1 At
the end of pregnancy the human corpus luteum has a diameter
not exceeding half-an-inch in length.
1 Schafer, Essentials of Histology, 7th Edition, London, 1907. The
similarity between the luteal and interstitial cells has also been remarked
upon by Allen, loc. cit.
154 THE PHYSIOLOGY OF REPRODUCTION
The corpus luteum of pregnancy is sometimes distinguished
from the structure formed when pregnancy does not supervene
after ovulation, the latter being called the false corpus luteum,1
or corpus luteum of menstruation ; but it is obvious that the two
bodies are identical in the early stages, and otherwise essentially
similar.2 Moreover, according to Ancel and Bouin,3 in animals
like the rabbit, which do not ovulate spontaneously during
oestrus, these two kinds of corpora lutea are identical throughout.
In such animals interstitial cells are believed to replace func-
tionally the " periodic corpus luteum/'
The hypotheses which have been put forward regarding the
function of the corpus luteum, and the possible part which this
organ plays in the metabolism of pregnancy, will be discussed at
some length in a future chapter. (For chemistry of corpus luteum
see p. 263.)
THE ATRETIC FOLLICLE
It has been already mentioned that the rabbit, the ferret, and
certain other animals do not necessarily ovulate during oestrus
in the absence of the male. The follicles, instead of bursting,
undergo degeneration (atresia) with their contained ova. Heape 4
has shown that the congested vessels in the wall of the follicle
may rupture and pour blood into the cavity, where it forms a
clot surrounding the degenerating ovum. The brilliant, suffused
red appearance of many of the rabbit's follicles during the early
stages of degeneration is said to result from internal bleeding.
The first rush of blood into the cavity washes away the
epithelium from the wall of the follicle, at the same time dis-
integrating the theca interna. Bleeding, however, does not
necessarily occur at all. In section the cavity of the degenerate
follicle appears, during the early stages, to be bounded by the
theca externa, while the ovum may be seen as a shrunken
object no longer enclosed by a discus proligerus.5 Heape 6
1 Or corpus luteum spurium.
2 The retrogressive changes are similar in both kinds of corpora lutea.
3 Ancel and Bouin, " Sur les Homologies et la Significance des Glandes
h, Secretion interne de 1'Ovaire," C. R. de la Soc. de BioL, vol. Ixvi., 1909.
4 Heape, "Ovulation, &c.," Proc. Roy. Soc., B., vol. Ixxvi., 1905.
5 Marshall, "The (Estrous Cycle in the Common Ferret," Quar. Jour.
Micr. Science, vol. xlviii., 1904. 6 Heape, loc. cit.
CHANGES IN THE OVARY
155
states that the contents of the follicle are gradually absorbed
through the agency of ingrowing parenchyma cells and leuco-
cytes. The cavity is eventually filled in by the ingrowth of
normal ovarian tissue.
The following characteristics serve to distinguish the de-
generate or atretic follicle (sometimes called the corpus luteum
atreticum) from the true corpus luteum : (1) There is no indi-
cation of any rupture to the exterior. (2) The ovum, being
retained in the follicle, loses its regularly circular shape, becomes
FIG. 38. — Section through follicle in early stage of degeneration. (From
Sellheim.) The ovum and follicular epithelium are in process of
atrophy.
shrivelled, and gradually disappears altogether. (3) The follicular
epithelium, instead of hypertrophying, degenerates, the chromatic
substance at one stage often appearing in the form of fine points
in the cytoplasm, and much smaller than nuclei. Subsequently
the remains of the cells become unrecognisable, finally disappear-
ing altogether. (4) The connective-tissue wall does not prolife-
rate to form a network among the epithelial cells, and there is
generally no ingrowth from the thecse until the epithelial cells
are in an advanced state of degeneration or have altogether dis-
appeared. The earliest indication of atretic change is usually
156 THE PHYSIOLOGY OF REPRODUCTION
seen in the chromatolytic changes in the epithelium. Afterwards
the theca interna degenerates, and then the ovum and zona
pellucida.
It should be mentioned, however, that the presence of a
degenerate ovum cannot, by itself, be regarded as an absolute
indication of follicular atresia, since Sobotta J has recorded in-
stances of rupture in the mouse and in the rabbit in which the
ova were accidentally retained within the cavity of the follicle,
the latter nevertheless forming an otherwise typical corpus
luteum ; and van der Stricht 2 has described a similar case of
retention in Vesperugo, in which part of the follicle was de-
generate while another part possessed the characteristic structure
of a corpus luteum.
Degeneration may set in at all stages in the development
of a follicle, and not merely in the fully formed follicle which
has failed to rupture. Loeb 3 has described follicular atresia
as being common in guinea-pigs of less than six months old.
The degenerative changes which such follicles pass through
have been studied in various Mammalia (chiefly rabbits, cavies,
and other Rodents) by Schulin,4 Flemming,5 Schottlander,6
Henneguy,7 Janosik,8 Kolliker,9 van der Stricht,10 Seitz,11 Loeb,
1 Sobotta loc. cit.
2 Van der Stricht, Une Anomalie interessante de Formation de Corps Jaunc,
Gand, 1901.
3 Loeb (L.), " tiber hypertrophische Vorgange bei der Follikelatresie,"
Arch.f. Mikr. Anat., vol. Ixv., 1905.
4 Schulin, "Zur Morphologic des Ovariums," Arch. f. Mikr. Anat., vol. xix.,
1881.
5 Flemming, " Ueber die Bildung von Richtungsfiguren in Saugethieren
beim Untergang Graafschen Follikel," Arch.f. Anat. u.Phi/s., Anat. Abth., 1885.
6 Schottlander, " Beitrag zur Kenntniss der Follikelatresie," &c., Arch.f.
Mikr. Anat., vol. xxxvii., 1891. " Ueber den Graafschen Follikel," &c., Arch.
/. Mikr. Anat., vol. xli., 1893.
7 Henneguy, " Recherches sur 1'Atresie des Follicules de Graaf," £c.,
Jour, de VAnat. et de la Phys., vol. xxx., 1894.
8 Janosik, "Die Atrophie der Follikel," Arch. f. Mikr. Anat., vol. xlviii.,
1896.
9 Kolliker, " Uber Corpora Lutea Atretica bei Saugethieren," Verhand. d.
Anat. Gesell., in Kiel, 1898.
10 Van der Stricht, "L'Atresie Ovulaire," &c., Verhand. d. Anat. Gcsell.,
in Bonn, 1901.
11 Seitz, "Die Follikelatresie wiihrend der Schwangerschaft," &c., Arch.
f. Oyndk., vol. Ixxvii., 1906.
CHANGES IN THE OVARY 157
and certain other writers, whose results are for the most part in
general agreement.
Schulin, and also Janosik, appear to regard the follicular^
epithelial cells as being converted into leucocytes, which they
undoubtedly resemble when undergoing degeneration. Flemming,
on the other hand, denies the existence of leucocytes, pointing out
P
:1^:
' -ftiS1^^^^^
mK^S^
& ' • • ^^^^&^
FIG. 39. — Section through follicle in late stage of degeneration. (From
Sellheim.) The cavity is in process of being filled by an ingrowth of
tissue from the wall. The ovum has disappeared.
that none exist in the theca, and Schottlander clearly distin-
tinguishes degenerating epithelial cells from leucocytes.
More recently, however, Dubuisson l has stated that in the
sparrow the follicle cells may multiply and act as phagocytes to
the yolk of the degenerating ovum, which becomes filled with
them. Afterwards they are said to migrate, leaving nothing
but connective tissue which fills in the cavity of the follicle. A
1 Dubuisson, "Contribution k 1'Etude du Vitellus," Arch, de Zool. Exper.,
vol. v., 5th series, 1906.
158 THE PHYSIOLOGY OF REPRODUCTION
similar process is described as occurring in certain reptiles.
Perez 1 also has recorded the phagocytic absorption of ova by
follicle cells in the ovary of the fasting newt.
Schottlander states that atresia can occur by fatty degenera-
tion as well as by chroma toly sis.
Flemming and others have described nuclear spindles in the
ova of follicles in an early stage of atresia, thus showing that
these had reached maturity before degeneration set in.
Atretic follicles may shrivel up rapidly, or continue for a time
in a cystic condition. In the latter case the cavity remains
filled with fluid. Kolliker has shown that certain of the cells
in the theca interna of cystic follicles may undergo a process of
hypertrophy ; and the same fact has been noticed by Seitz, who
calls these cells " theca lutein cells" owing to their resemblance
to the cells of the corpus luteum. Seitz found these cells only
during pregnancy.
Heape 2 has shown that in the rabbit two kinds of degenera-
tion prevail. In the one kind ; the changes first affect the follicle
and then the ovum, as described above. In the other the ovum
is first affected and the follicle afterwards. Heape interprets
the latter change as evidence that the ovum is not capable of
assimilating the nourishment supplied to it.
Atresia is commonly stated to occur most frequently during
pregnancy, but it may occur at other times.3 Thus Sandes 4 has
shown that in Dasyurus, as soon as the corpus luteum is formed,
the surrounding follicles which were previously in various stages
of active development begin to undergo atrophy. The process
begins in the follicles in closest proximity to the newly formed
corpus luteum, and is continued during pregnancy in the other
follicles in ever-widening circles. Sandes suggests that this
occurs as a result of mechanical pressure due to the growth of
the corpus luteum, or is in some way effected by the internal
secretion which the latter organ is supposed to elaborate.
Heape 5 states that in the case of the rabbit, if the buck is with-
1 Perez, " Sur la Resorption phagocytaire des Ovules," &c., Proces-
Verkaux de la Soc. des Sciences de Bordeaux, 1903.
2 Heape, loc. cit.
3 Marshall, "The (Estrous Cycle. &c., in the Sheep," Phil. Trans., B.,
vol. cxcvi., 1903.
4 Sandes, loc. cit. 5 Heape, loc. cit.
CHANGES IN THE OVARY 159
held from a doe during several consecutive oestrous periods,
not merely the majority of the older follicles degenerate, but
also many of the younger ones, so that the animal is liable to
become sterile during the remainder of the breeding season.1
There can be little doubt that the more usual cause of de-
generation in immature follicles is lack of sufficient nutriment, or
of nutriment of the requisite kind. It is usually to be observed
in under-fed animals, or in animals living under unsuitable con-
ditions, but it also occurs in very fat animals. Ewart states
that follicular degeneration tends to occur in mares leading a
semi- wild life in winter.2 Probably it is least common in animals
which are in a good thriving condition, but further investigation
is urgently needed before these points can be decided.
SUPERFCETATION
In the majority of Mammals, as in Dasyurus, there can be
little doubt that the presence of the corpus luteum tends to
produce follicular degeneration, or at any rate to inhibit matura-
tion. In the mare, however, Ewart has shown that degeneration
does not generally take place during early pregnancy, so that
if a mare aborts (a common occurrence with this animal) ripe
ova are available for fertilisation, and pregnancy can be started
anew without delay.3
If ovulation takes place during pregnancy, and if, owing to
the occurrence of coition (see p. 51) the ova become fertilised,
the phenomenon of superfoetation may take place — that is to
say, foetuses of different ages may be present in the same uterus
—but this condition is of course abnormal, though it has been
known to occur in several animals. Thus, Mr. W. 0. Backhouse
has informed me of a case of a cat which experienced heat and
underwent coition after being pregnant for six weeks, and three
weeks later produced five kittens, four of which were of the
normal size and were obviously born at full time (dating from
the heat period prior to the beginning of pregnancy), whereas
1 Cf. Dubreuil and Eegaud (C. E. de la Soc. de Biol., vol. Ixvii., 1909),
who say that absence of sexual intercourse causes hseinorrhage in the
follicles.
2 Ewart, loc. cit. 3 Ibid.
160 THE PHYSIOLOGY OF REPRODUCTION
the other kitten was very small, and apparently about three
weeks developed.
FORMATION OF OVA
It is usually stated that all the ova which are to be de-
veloped in the ovary exist in it at the time of birth, and that a
considerable proportion of these undergo atrophy before puberty.
Thus, the number of ova in the ovary at birth has been estimated
at 100,000, of which it is supposed that not more than 30,000
remain at puberty.1
Miss Lane-Claypon,2 however, has described the formation of
ova, resembling primordial ova, from interstitial cells during
adult life. These cells are shown to increase markedly in size,
their length being often almost doubled. In addition to their
becoming enlarged, certain of the interstitial cells near the
periphery undergo further changes during the later stages of
pregnancy. The cells appear to pass outwards and become cut
off by connective tissue, and in many cases almost reach the
surface of the ovary. This process begins in the rabbit at
about the twentieth day of pregnancy. A little later some of
the cells appear to be multi-nucleated, and it is suggested that
these are formed by the fusion of the same number of inter-
stitial cells as there are nuclei. The nuclei then degenerate
with the exception of one, and the inference is drawn that the
latter lives and grows at the expense of the others in just the
same way as Balfour concluded that one developing ovum in
the immature ovary might be nourished by the surrounding
ova which were undergoing degeneration.
In the ovary of a rabbit whose time of parturition had nearly
arrived, the interstitial cells were observed to have undergone
further changes identical with those taking place in the deuto-
broque cells of a young ovary during the period of oogenesis (see
above, p. 120). The leptotenic stage is rapidly passed through
and the nucleus enters upon the synaptenic condition, which
1 Galabin, A Manual of Midwifery, 6th Edition, London, 1904. Accord-
ing to another calculation the human ovary at the age of seventeen contains
17,600 ova (Heyse, Arch. f. Gynak., vol. liii., 1893), of which only 400
become mature (Henle, Handbuch der Anatomic, 1873).
2 Lane-Claypon, " On the Origin and Life-History of the Interstitial Cells
in the Ovary in the Rabbit," Proc. Roy. Soc., B., vol. Ixxvii., 1905.
CHANGES IN THE OVARY 161
extends over a somewhat longer time. The massing of the
chromatin into a lump having been completed, it again becomes
spread out and rearranged, and the pachytenic stage is entered
upon. The chromatin filaments during this stage are markedly
thicker and more bulky. It is followed by a not very typical
diplotenic stage, in which the duality of the filaments is said to
be not well shown. In the next stage — the dictyate stage —
the nucleolus becomes very definite, and the chromatin is
arranged more or less over the entire nuclear area, which is now
of considerable dimensions. ' There can be ... not much
doubt that the changes taking place are identical with those
seen in the young ovary, which lead to ovogenesis, and there-
fore it would appear that ovogenesis also takes place in the
adult animal during pregnancy." l
Thus it would seem that the interstitial cells, which, like the
ova, are almost certainly derived from the germinal epithelium,
are actually potential ova, being capable of developing into true
ova when the appropriate stimulus is given. This stimulus is
provided by pregnancy, at which period they undergo enlarge-
ment so as to exceed the size of a primordial ovum, and in
addition pass through the same series of nuclear transformations
as those which characterise embryonic oogenesis.2
THE SIGNIFICANCE OF THE PROCESTROUS CHANGES
Having discussed the conditions under which the Graafian
follicles ripen and discharge in various species of the class
Mammalia, we are now in a position to consider more fully the
significance of the uterine changes with which ovulation is
frequently associated.
Many obstetricians have adopted the view that the de-
generation stage of menstruation in the human female is of the
nature of an undoing of a preparation (represented by the
1 Lane- Clay pon, loc. cit.
2 For an account of the interstitial tissue of the ovary in various animals,
see Fraenkel. See also Cesa-Bianchi, who states that the interstitial ovarian
gland in hibernating animals undergoes a great development in spring and
summer, but is much reduced in winter. He also comments on the close
resemblance between luteal and interstitial cells. (" Vergleichende histo-
logische Untersuchungen iiber das Vorkommen drusiger Formationen im
iuterstitiellen Eierstockgewebe," Arch. f. Gynak., vol. Ixxv., 1906.)
L
162 THE PHYSIOLOGY OF REPRODUCTION
previous growth stage) for an ovum which failed to become
fertilised (or even to be released from the ovary). This theory
was originally put forward by Sigismund,1 and was subsequently
accepted by His.2 It has been summarised in the well-known
dictum that " women menstruate because they do not conceive/'
It has been shown above, however, that menstruation in the
Primates is the physiological homologue of the procestrum in the
lower Mammalia, and that ovulation in the latter occurs usually,
so far as is known, during oestrus, or at any rate not until after
the commencement of the destruction stage of the procestrum.
Consequently Sigismund's theory becomes untenable.
Loewenthal 3 advanced the somewhat similar theory that the
monthly bleeding is actually brought about by the death of the
ovum in the uterus, the " decidua " of menstruation being pro-
duced by the embedding therein of the unfertilised egg. No
evidence has been adduced in support of this view, which is
evidently open to the same objection as Sigismund's hypothesis.
A further modification of the same theory has been ad-
vanced by Beard,4 who expresses the belief that the process of
menstruation is of the nature of an " abortion of something
prepared for an egg given off at or after the close of the pre-
ceding menstruation, and [that] it takes place because this egg
has escaped fertilisation." " Prior to the appearance of the
menses the uterus has formed a decidua, which is regarded as
equivalent to that which would arise when a fertilised egg be-
came affixed to the uterus/' This theory also, if it is to be
entertained at all, necessitates the assumption that there is no
correspondence between the prooestrum in the lower Mammalia
and menstruation in the Primates, since the degeneration stage
of the procestrum in the dog or ferret, for instance, can hardly
be of the nature of an abortion of something prepared for an
ovum which was discharged at the preceding " heat period "
many months before. The difficulty is further increased for
those animals which experience oestrus only once a year, or even
1 Sigismund, "Ideen iiber das Wesen der Menstruation," Berliner Klin.
Wochenschr., 1871.
2 His, Anatomie Menschlicher Embryonen, 1880.
3 Loewenthal, " Eine neue Deutung des Menstruationsprocesses,"Jrc&. /.
Gynak., vol. xxiv., 1884.
4 Beard, The Span of Gestation and the Cause of Birth, Jena, 1897.
CHANGES IN THE OVARY 163
less often, for it is improbable that they ovulate more frequently
than they come " on heat." Beard, however, denies that there
is any correspondence between " the heat or rut of Mammals ^_
and menstruation in the higher forms, saying that very little is
required in disproof of the supposed relation.
The theory that the whole procestrous process, including both
the degeneration and the recuperation stages, is of the nature of
a preparation 1 on the part of the uterus for the reception of a
fertilised ovum is not opposed to any of the known facts. The
process is sometimes viewed as a kind of surgical " freshening "
of the uterus, whereby the ovum can be safely attached to the
mucosa during the healing stage. It is possible, however, that
the changing of the uterine tissue is not the least important part
of the process.
Emrys-Roberts 2 has made the further suggestion that the
secretion of the uterine glands, together with the blood and other
products of procestrous destruction, may serve to provide a rich
pabulum on which to nourish the embryo during the earliest
days of pregnancy.
In opposition to these theories it may be urged that pregnancy
has been known to take place in women who have never
menstruated, and that it may occur during periods of amenorrhoea,
or during the lactation period, when menstruation is sometimes
in abeyance. Such cases, however, are the exception, and it
must not be inferred that because the prooestrous function can
occasionally be dispensed with without inducing a condition
of sterility, it normally plays no part in the physiology of
generation.
It has been pointed out, however, that the severity of the
menstrual process in women is occasionally so great as to be
positively injurious, and that such cases evidently belong to the
category of constitutional disharmonies which Metchnikoff 3
1 Kundrat and Engelmann, " Untersuchungen iiber die Uterusschleim-
haut," Strieker's Med. Jahr., 1873. Lawson Tait, Diseases of Women, 1889.
For a further discussion of some of the theories regarding the purpose of
menstruation see Heape, " The Menstruation of Semnopithecus entellus" Phil.
Trans. £., vol. clxxxv., 1894.
2 Emrys-Roberts, " A Preliminary Note upon the Question of the Nutri-
tion of the Early Embryo," Proc. Roy. Soc. B , vol. Ixxvi., 1905.
3 Metchnikoff, The Nature of Man, London, 1903.
164 THE PHYSIOLOGY OF REPRODUCTION
has shown to be so common in the organs and functions of the
generative system.
Geddes and Thomson l also have called attention to the
pathological character of menstruation, as evidenced not only
by the pain which frequently accompanies the process, and the
local and constitutional disorders by which it is often attended,
but by the general systemic disturbance which always occurs
synchronously with it. These authors interpret the discharge
as a means of disposing of the anabolic surplus which is con-
sumed during pregnancy by the developing embryo. A similar
view is adopted by Webster,2 who associates the introduction
of menstruation (as distinguished from the procestrum of the
lower animals) with a diminished fertility.
Reference has already been made to the " Wellenbewegung "
or " wave " hypothesis regarding the nature of menstruation
(see p. 67).
The physiological cause of the prooestrum, and the probable
part played by the ovaries in this connection, will be discussed
at some length in a later chapter.
1 Geddes and Thomson, The Evolution of Sex, Revised Edition, London,
1901.
2 Webster, " The Biological Basis of Menstruation," Montreal Med. Jour.,
April 1897.
CHAPTER V
SPERMATOGENESIS— INSEMINATION
" Denique per maria ac mentis fluviosque rapacis
Frondiferasque domos avium camposque virentis,
Omnibus incutiens blandum per pectora amorem
Efficis ut cupide generatim sascla propagent."
— LUCRETIUS.
THE spermatozoa, or reproductive cells of the male, were ob-
served as far back as the year 1677, when Hamm, who was a
pupil of Leeuwenhoek, directed the latter's attention to them.
Leeuwenhoek, however, did not understand the significance of
what he saw.
Spallanzani 1 was the first to show that the presence of
spermatozoa in the semen was an essential factor in fertilisation,
since the filtered fluid was found to be impotent. Subsequently
Kolliker 2 discovered that the sperms arise from the cells of the
testis, and Barry 3 observed the conjugation of sperm and ovum
in the rabbit.
Van Beneden's discovery that the nuclei of the conjugat-
ing cells — both ova and spermatozoa — contain only half the
number of chromosomes that they had originally has been
referred to in the preceding chapter, where the maturation
phenomena in the ovum have been briefly outlined4 (p. 130).
The four products of division formed at the completion of re-
duction in the male differ from those in the female in that each
of them is a functional conjugating cell. Before describing the
reduction process in detail it will be well to give a short account
of the structure of the testis.5
1 Spallanzani. Dissertations, English Translation, vol. ii., London, 1784.
2 Kolliker, Beitrdge zur Kcnntniss dcr Gcschlcchtsvcrhaltnisse, &c., Berlin, 1841.
3 Barry (M.), " Spermatozoa observed within the Mammiferous Ovum," Phil.
Trans., 1843.
4 For accounts of the history of the chief discoveries relating to the
spermatozoa, fertilisation, &c., see Thomson, The Science of Life, London,
1899, and Geddes and Thomson, The Evolution of Sex, 2nd Edition,
London, 1901.
5 See Barry (D. T.), " The Morphology of the Testis," Jour, of A not. and
Phys., vol. xliv., 1910.
165
166 THE PHYSIOLOGY OF REPRODUCTION
This organ is enclosed within a fibrous capsule, the tunica
albuginea, which is very rich in lymphatics. It is covered by
a layer of serous epithelium reflected from the tunica vaginalis.
Posteriorly the capsule is prolonged into the interior of the
testis in the form of a mass of fibrous tissue (the mediastinum
testis). Certain other fibrous processes or trabeculae also pro-
FiG. 40. — Section through human testis and epididymis. (After Bohm
and von-Davidoff, from Schafer.)
a, glandular substance divided into lobules by septa of connective tissue ;
b, tunica albuginea; c, part of epididymis; d, rete testis; e, body of
epididymis ; /, mediastinum ; g, sections through commencing portion
of vas deferens.
ject inwards from the capsule, and divide the glandular substance
into lobules. The efferent ducts of the testis (vasa efferentia)
open into a single convoluted tube situated at the posterior
margin of the organ and attached to the mediastinum. This
is the epididymis. Its lower extremity is prolonged into a
thick-walled muscular tube (the vas deferens) which is the
SPERMATOGENESIS —INSEMINATION
167
passage of exit for the seminal fluid or sperm-containing secretion.
The glandular substance of the testis is composed of the con-
FIG. 41. — Section through testis of monkey.
a, seminiferous tubules ; b, interstitial tissue ; c, rete testis ; rf, vasa
efferentia ; e, vas deferens ; /, tunica albuginea.
voluted seminiferous tubules, two or three of which join together
to form a straight tubule which passes into the body of the
mediastinum. The straight tubules within the mediastinum
168 THE PHYSIOLOGY OF REPRODUCTION
unite in their turn, giving rise to a network of vessels called the
rete testis. From the rete the vasa efferentia are given off.
Between the tubules is a loose connective tissue containing a
number of yellow epithelioid interstitial cells. The connective
tissue also contains numerous lymphatics and blood-vessels
(branches of the spermatic artery). The nerves of the testis
are derived from the sympathetic system, but a few filaments
come from the hypogastric plexus.
In embryonic development the tubules arise from the
primitive germinal epithelium. According to Allen 1 the inter-
stitial cells are derived from connective tissue.
The straight tubules, and the tubules of the rete, are lined by
a single layer of cubical or flattened epithelium without a base-
ment membrane. The seminiferous tubules, on the other hand,
contain several layers of epithelial cells supported by a thick
basement membrane. The layer nearest the membrane con-
sists of clear cubical cells, a few of which show evidence
of division. These are the spermatogonia. Certain of the
epithelial cells between the spermatogonia are enlarged, and
project among the more internal cells in association with de-
veloping sperms. These are the cells of Sertoli. On the inside
of the spermatogonia are certain larger cells, known as sperma-
tocytes. These are products of division of spermatogonia, each
of which on dividing into two gives rise to a cell like itself,
and another cell, which grows larger, passes into the second layer,
and becomes a spermatocyte.
The spermatids, which in some seminiferous tubules lie on the
inside of the spermatocytes, are the double products of division
of the latter. The spermatids so formed may be seen as small
cells with spherical nuclei, and forming irregular clumps on the
inner surface of the tubule. Often, however, the spermatids
are elongated, being partially converted into spermatozoa. As
this process of transformation proceeds, the developing sperms
become arranged in little groups. Associated with each group
is a foot-cell, or a cell of Sertoli, which probably serves as a
1 Allen, "The Embryonic Development of the Ovary and Testis," Amer.
Jour, of Anat., vol. iii., 1904. As already mentioned, Allen regards the in-
terstitial cells of the ovary as being developed from connective tissue, thus
differing from Miss Lane- Clay pon.
SPERMATOGENESIS— INSEMINATION
169
support and as a means of conveying nourishment to the growing
spermatozoa.1 The tails of the latter at this stage project
freely into the cavity of the tubule, and a little later the sper-
matozoa shift bodily forward and become completely liberated.
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FIG. 42.— Section through portion of two seminiferous tubules in testis
of rat.
a, basement membrane ; &, spermatogonium ; c, spermatocyte ; d, sper-
matozoa in cavity of tubule ; e, interstitial tissue containing vessels.
1 Merkel, " Die Stiitzellen des Menschlichen Hodens," Mailer's Archiv,
1871. Brown, "On Spermatogenesis in the Eat," Quar. Jour. Micr. Science,
vol. xxv., 1885. Bende, " Untersuchungen iiber den Bau den Funktioniren den
Samenkaniilchens einiger Siiugethiere," Arch. f. Mikr. Anat., vol. xxx
1887.
170 THE PHYSIOLOGY OF REPRODUCTION
According to Loisel,1 the orientation of the sperms in the testis
is due to a secretion from the cells of Sertoli, together with
FIG. 43.— A cell of Sertoli with which the spermatids (three of which are
shown) are beginning to be connected — human. (After Bramman. from
Schafer.) The cell contains globules of nutritive substance and similar
smaller globules are seen in the spermatids.
FIG. 44.— Diagram illustrating the cycle of phases in spermatogenesis.
(From Schafer.)
a, spermatogonia (seen dividing at 6) ; a', a", Sertoli cells; 6, spermatocytes
(seen dividing at 5) ; c, spermatids ; s', parts of spermatids which dis-
appear when spermatozoa are fully formed ; s, seminal granules.
1 Loisel, " Facteurs de la Forme et de la Fasciculisation des Spermies
dans les Testicules," Jour, de I'Anat. et de la Phys., vol. xlii., 19C6.
SPERMATOGENESIS— INSEMINATION 171
certain of the other cells in the parietal layer of the seminiferous
epithelium.
In male animals which have a rutting season spermatp-_
genesis occurs only at this time. At other seasons of the year
the testes remain in a quiescent condition.1 The periodic
activity of the testis is usually correlated with a great increase
in the size of that organ (see pp. 24 and 61).
Spermatogonium. Oogonium.
Proliferation
period.
Growth period.
Maturation
period.
FIG. 45. — Scheme of spermatogenesis and oogenesis. (After Boveri.)
The changes which occur in spermatogenesis may be sum-
marised as follows : (1) A spermatogonium divides into two,
one product of division passing into the second layer of the
seminal epithelium and becoming a spermatocyte. (2) A
1 In some animals the renewal of activity in the testes is associated with
the descent of these organs from their position in the abdominal cavity
through the inguinal canal and into a cutaneous fold. This is transformed
into the scrotum, which lies behind the penis (except in Marsupials, where it
is in front). In many Mammals the descent takes place at an early age and
is permanent. In others (most Kodents, Insectivores, and bats) the testes
are withdrawn into the abdominal cavity after the breeding season is over.
This is effected by the cremaster muscle.
172 THE PHYSIOLOGY OF REPRODUCTION
spermatocyte, or mother-cell, divides. (3) A product of division
of a spermatocyte divides, giving rise to a spermatid, the number
of chromosomes becoming reduced during this process to one-
half the previous number. Subsequently the spermatid elongates,
the nucleus becomes shifted to one end, and the spermatozoon
which is formed in this way is set free. The process is con-
tinually going on in the seminiferous tubules of the testis, suc-
cessive crops of spermatozoa being from time to time produced.
The various stages of development may generally be observed
in the same testis, or even within the limits of a single tubule.
It is supposed that the reduction in the number of the
chromosomes is a preparation of the conjugating cells for their
subsequent union in fertilisation, and is a means by which this
number is held constant in the species (see p. 131). l In those
animals in which reproduction is normally effected without the
intervention of a spermatozoon (parthenogenesis) the ovum
may discharge only one polar body instead of two.
STRUCTURE OF SPERMATOZOA
A fully developed human spermatozoon consists of a
flattened egg-shaped head, a short cylindrical body or middle-
piece, and a long delicate vibratile tail. Lying anterior to the
head is a small apical body, or achrosome, which in some animals
bears a little barb-like projection by means of which the sper-
matozoon bores its way into the ovum. The tail of the sperm
consists of an axial filament surrounded by a protoplasmic
envelope, which becomes very thin or disappears altogether at
the extremity, leaving a short naked end-piece. The axial
filament passes anteriorly through the middle-piece, and ends
in a small knob (the end-knob) at the base of the head.
Ballowitz 2 has shown that the axial filament is composed of a
number of parallel fibrilla?, like a muscular fibre.
1 For an account of the process of spermatogenesis in different animals
and plants, and a discussion of the phenomena described, see Wilson,
The Cell in Development and Inheritance, 2nd Edition, London, 1900.
In this work the theories of Weismann and others are dealt with, and a
full account of the literature is given.
2 Ballowitz, " Untersuchungen liber die Struktur der Spermatozoon,"
Arch. f. Mikr. Anat., vol. xxxii., 1888, and vol. xxxvi., 1890; Zeitschr. f. wiss
Zool, vol. lx., 1890, and vol. Hi., 1891.
SPERMATOGENESIS— INSEMINATION
173
Schweigger-Seidel l and La Valette St. George 2 were the first
to prove, independently but almost simultaneously, that the
FIG. 46. — Human spermatozoa on the flat and in profile. (After Bramman,
from Schafer.) x 2500. Those on the right have adhering protoplasm.
The tail is only partly shown in the two seen in profile.
1 Schweigger-Seidel, " Uber die Samenkorperchen und ihre Entwickelung,"
Arch. f. Mikr. Anat., vol. i., 1865.
2 La Valette St. George, " Dber die Genese der Samenkorper," Arch. f.
Mikr. Anat., vol. i., 1865.
174 THE PHYSIOLOGY OF REPRODUCTION
spermatozoon has the essential characteristics of a complete cell.
The head contains the nuclear material, which is surrounded by
a thin layer of cytoplasm. The end-knob is said to represent
the centrosome.
Spermatozoa, conforming with more or less closeness to the
type described above, occur in the greater majority of multi-
cellular animals from the Ccelenterata up to Mammals. In
! 2 Pisces, and also in Echinoderms, the
general resemblance is very distinct, but
in other forms of life there is more
diversity in the form assumed by the
spermatozoa. ''' The head (nucleus) may
be spherical, lance-shaped, rod-shaped,
spirally twisted, hook-shaped, hood-
shaped, or drawn out into a long
filament ; and it is often divided into
an anterior or a posterior piece of
different staining capacity, as is the
case with many birds and Mammals.
The achrosome sometimes appears to
be wanting, e.g. in some fishes. When
present, it is sometimes a minute
rounded knob, sometimes a sharp stylet,
and in some cases terminates in a sharp
barb-spur by which the spermatozoon ap-
pears to penetrate the ovum (Triton)." 1
The middle-piece also shows considerable
variability. It may be spherical, cylin-
drical, or flattened against the nucleus ;
sometimes it is of great length, and
sometimes it passes insensibly into the flagellum or tail. The
latter, in some insects and fishes, gives attachment to a mem-
branous fin. The end of the axial filament, as already mentioned,
is sometimes left naked, giving rise to the end-piece.
The tadpole-like shape is not an essential characteristic of
the spermatozoon, for in certain Arthropods and Nematodes
there is no flagellum, and the sperms are consequently incapable
of spontaneous movement. In the daphnid Polyphemus the
1 Wilson, loc. cit.
FIG. 47. — Human sperma-
tozoa ( x 1000). (After
Retzius, from Scha-
fer.)
1, in profile ; 2, view on
the flat ; I, head ; c,
middle-piece ; d, tail ;
e, end-piece of tail,
described as a dis-
tinct part by Retzius.
SPERM ATOGENESIS— INSEMIN ATION
175
sperms are said to be amoeboid. In some crustacean sperma-
tozoa there are a number of radiating spine-like processes
which seem to take the place of the flagellum.
In other animals, and notably in the gasteropod mollusc
Paludina, there are two kinds of spermatozoa. In this animal
one is of the usual type, whereas the other is larger and worm-
shaped, with a tuft of cilia at one end. The smaller variety
alone is said to be functional.1
The size of the sperm varies greatly in different animals.
In Man its length is about '05 millimetres or a 300th of an inch,
il & ft
a
d
FIG. 48.— Different forms of spermatozoa from different species of animals,
as follows : —
a, bat ; b & c, frog ; d, finch ; e, ram ; / & g, boar ; 7t, jelly-fish ;
i, monkey ; k, round worm ; I, crab. (From Verworn.)
the head and the middle-piece being each about '005 millimetres
long.
It is obvious that the sperm contributes comparatively little
material to the fertilised ovum, being provided with only suffi-
cient protoplasmic substance to form a locomotive apparatus
by means of which it gains access to the ovum. The pre-
dominantly destructive metabolism of the spermatozoon as con-
trasted with the ovum has been strongly emphasised by Geddes
and Thomson,2 who believe it to exemplify those katabolic
1 For further details of the structure of various kinds of sperms see
Wilson, loc. cit. ; also Ballowitz's papers just referred to, and Retzius'
Biologische Untersuchungen, vols. xi., xii., and xiii., Stockholm and Jena.
The latter contains numerous large plates with figures of spermatozoa.
- Geddes and Thomson, The Evolution of Sex, Revised Edition, London,
1901.
176 THE PHYSIOLOGY OF REPRODUCTION
phenomena which, according to their view, are usually associated
with the male sex.
SEMINAL FLUID
The semen serves as the mechanical medium in which the
spermatozoa move. It is possible also that it has a nutritive
function. It is secreted by the seminiferous tubules. It is milky
in appearance, and has a characteristic smell. When ejected the
seminal fluid is mixed with the secretions of the accessory
glands (prostate, &c.), which render it still more milky. On
standing it tends to become gelatinous. According to Lode,1
the specific gravity of semen is between 1'027 and 1'046.
The number of spermatozoa which exist in normal human
semen is subject to much variation. Lode 2 has shown that it-
diminishes almost to zero after a number of successive emissions,
but increases again after an interval of several days. The average
number is given as 60,000 per cubic centimetre. The number
of sperms present in the ejected seminal fluid of the dog was
also found to be greater at the end of an interval in which there
were no emissions, but it did not continue to increase after more
than eight or ten days. In a normal emission of semen (Man)
Lode calculates that there are about 226,000,000 spermatozoa,
but that the number may vary from zero to 551,000,000.
The spermatozoa which are not ejaculated degenerate.
The tails break off, and undergo a gradual liquefaction. The
end products are ultimately absorbed by the epithelial cells of
the seminal vesicles, and perhaps by the cells of the vasa de-
ferentia or of the testis itself. According to Perez,3 the sperma-
tozoa of male newts which are kept apart from females are
absorbed by phagocytes.4
MOVEMENTS OF SPEBMATOZOA
When the spermatozoa are in the testis they are inactive, but
they begin to move rapidly as soon as they are ejected in the
1 Lode, " Untersuchungen uber die Zahlen- und Regenerationsverhaltnisse
der Spermatozoiden bei Hund und Mensch," Pjlugers Arch., vol. 1., 1891.
2 Lode calculates that about 339,385,500,000 spermatozoa must be pro-
duced in man between the ages of twenty-five and fifty-five.
3 Perez, " R^sorption phagocytaire des Spermatozoides," Proces-Verbaux
de la Soc. das Sciences de Bordeaux, 1904.
4 The chemistry of the spermatozoon and semen is dealt with in
Chapter VIII.
SPERMATOGENESIS— INSEMINATION 177
seminal fluid. The rate at which they progress has been
estimated at 3*6 millimetres per minute.1 Bischoff 2 found
spermatozoa at the top of the oviduct in the rabbit nine or ten
hours after coition.
It is probable that the ejected spermatozoa continue to
undergo movement, as a general rule, so long as they retain
their vitality, the rate of movement becoming gradually
diminished and ceasing altogether shortly before death. In
bats, however, during the period of hibernation the sperms
become quiescent without dying, their vigour being restored
in the spring when they conjugate with the ova.3 It is
exceedingly probable also that in the spotted viviparous
salamander and the other animals referred to below (p. 186), in
FIG. 49.— Diagram illustrating wave-like movement of swimming
spermatozoon. (From Nagel.)
which the male cells retain their vitality for long periods, these
must at such times remain quiescent, for otherwise their store
of energy would soon become exhausted.
The spermatozoa swim by means of their tails. The move-
ment is represented in the accompanying figure (taken from
Nagel),4 which shows the successive positions assumed by the
sperm in a state of locomotion. A wave of movement first
makes its appearance in the forepart of the tail, and then rapidly
travels backwards to the end, to be succeeded by a fresh wave
which follows the same course. It would seem that the driving
1 Lott, Anatomic und Physiologic des Cervix Uteri, Erlangen, 1871. Ac-
cording to Adolphi ("Ueber das Verhalten von Schlungenspermien in
stromender Flussigkeiten," Anat. Anz., vol. xxix., 1906), the spermatozoa of
the adder swim at the rate of 50 p. to 80 /*. per second.
2 Bischoff, Die Entwickelung des Kaninchen-Eies, Giessen, 1842
3 See p. 136.
4 Nagel, Handbuch der Physiologic des Menschen, vol. ii., Braunschweig,
1906.
M
178 THE PHYSIOLOGY OF REPRODUCTION
force is located a little behind the head. The head itself
does not appear to be concerned in the movements of
locomotion.
The movements of spermatozoa have probably been studied
most closely in Insecta and Echinodermata. Buller 1 says that
the sperms of the Echinoidea in a drop of sea-water (or the
medium in which they are normally discharged) swim spirally,
so long as they do not come into contact with the surface. The
spirals may be so steep that the sperms appear to move almost
in a straight line, in which case progression across the field of
the microscope is relatively rapid. In other cases the incline
of the spiral is so slight that the spermatozoa swim almost in
circles, and consequently move forward across the microscopic
field with great slowness. Every gradation between these two
extremes was observed, but the more active sperms generally
swam in the steeper spirals.
Dewitz 2 has shown that when the spermatozoa of the cock-
roach are put into 0'6 per cent, solution of sodium chloride, and
placed between two surfaces, such as those of a slide and a
cover-glass, they collect after a short time, partly upon the
upper surface of the slide and partly upon the lower surface of
the cover-glass. In these positions they describe circles with
their tails, the rotation being invariably counter-clockwise.
The bulk of the liquid remains free from spermatozoa, the latter
adhering to the glass surfaces after having once reached them.
If a ball be placed in the fluid, its surface is soon sought by the
spermatozoa.3 Verworn has described this phenomenon under
the name of " baro taxis," and states that it is caused by pressure
acting unequally on different sides of the spermatozoon. It is
said to be of great importance in the process of fertilisation,
and probably assists the spermatozoon in entering the micropyle
1 Buller, " Is Chemotaxis a Factor in the Fertilisation of the Eggs of
Animals ? " Quar. Jour. Micr. Science, vol. xlvi., 1902.
2 Dewitz, " Ueber Gesetzmassigkeit in der Ortsveranderung der Sper-
matozoen," &c., Pfliigers Archiv, vol. xxxviii., 1886. Rotation by spermatozoa
seems to have been recorded first by Eimer, " Untersuchungen iiber den
Bau und die Bewegung der Samenfaden," Verhand d. Phys. Med. OeseL zur
Wiirzburg, vol. vi., 1874.
3 Ballowitz, " Untersuchungen iiber die Struktur der Spermatozoon,"
&c., Zeitschr.f. ZooL, vol. i., 1890.
SPERMATOGENESIS— INSEMINATION 179
of the ovum.1 Dewitz's observations were subsequently con-
firmed by Ballowitz.2
Counter-clockwise rotation upon surfaces was first recorded
for the spermatozoa of Echinoderms by Dungern,3 who dis-
covered the phenomenon in Sphcerechinus and Arbacia. About
the same time Buller,4 who has described the manner of rotation
more fully, observed its occurrence in the sperms of various
other Echinoderms, and particularly in those of Echinus :
;" When a spermatozoon comes in contact with a glass surface,
unless it becomes immediately fixed to the glass [it] begins to
make characteristic circular revolutions upon it. If the cover-
glass be supported by pieces of another cover-glass, and the
upper surface of the drop in contact with it be carefully focussed,
it is seen that all the spermatozoa which are not attached by
their heads, but are moving there, are revolving from the
observer's point of view in clock- wise direction. If the lower
surface of the drop in contact with the slide be examined, a
reverse rotation — the counter-clockwise — is seen to be the rule.
In both cases, therefore, if the surfaces be regarded from the
point of view of the spermatozoa, the rotation is always in one
direction — namely, the counter-clockwise/'
The head is the only visible part of the rotating spermatozoon.
This moves rapidly round in a circle, which in the case of
Echinus is slightly less than O05 millimetres (or the length of
a spermatozoon) in diameter. A normally rotating sperm of
Sphcerechinus was observed to make 109 circles around one
point in ninety seconds. The rate of movement of the head is
calculated to be about 0'12 millimetres per second, or 7 '2 milli-
metres per minute.
The characteristic rotation may likewise take place upon
surfaces which are bounded by air (instead of glass), and it has
been observed also upon the outer surface of the gelatinous
layer of the ova of Echinus. Buller concludes, therefore, that
the nature of the surface is not an important factor in the process.
1 Verworn, General Physiology, Lee's Translation from the second German
Edition, London, 1899.
2 Ballowitz, loc. cit.
3 Dungern, "Die Ursachen der Specietat bei der Befruchtung," Zentralbl.
f. Physiol,, vol. xv., 1901.
4 Dungern, loc cit.
180 THE PHYSIOLOGY OF REPRODUCTION
Ballowitz expresses the opinion that the circles described
by insects' sperms are simply the modified spirals made by the
free-swimming cells. Buller thinks that this view, which pro-
vides a purely mechanical explanation, is also probably correct
for the spermatozoa of Echinoderms.
Since counter-clockwise rotation upon surfaces has been
observed in the spermatozoa of two groups as widely separate
as the Insecta and the Echinodermata, it would seem probable,
as Buller remarks, that it will be found to occur in other animals.
The spermatozoa of Mammals, in traversing the female
passages after copulation, make their way upward towards the
ovaries in opposition to downward currents set up by the cilia
of the lining epithelia. Kraft l has shown that when rabbits'
spermatozoa, in a state of feeble motion, are placed upon the
inner wall of the oviduct, their movements become more
vigorous and they swim against the current which the cilia pro-
duce. Roth 2 also has succeeded in experimentally illustrating
the same fact.
It is commonly stated that in Man the passage of the sperma-
tozoa from the vagina inwards is assisted by a contraction of
the muscular wall of the uterus, which compresses the cavity of
that organ into which the sperms are drawn when relaxation
takes place.3 The contraction of the uterus is said to be a
reflex action resulting from copulation. It has also been sug-
gested that, during copulation, a mucous plug which is ordinarily
contained in the cervix may be temporarily and partially ex-
pelled into the vagina and afterwards withdrawn with the
spermatozoa adhering to it.4
So also Heape 5 has shown that in the rabbit the passage of
the spermatozoa into the uterus is probably assisted by a sucking
1 Kraft, " Zur Physiologic des Flimmerepithels bei Wirbelthieren."
Pfliiger's Archiv, vol. xlvii., 1890.
2 Both, " Ueber das Verhalten beweglicher Mikroorganismen in stroraender
Fliissigkeit," Deutsche med. Wochenschrift, vol. xix., 1893. Verworn (loc. cit.)
describes this property of spermatozoa under the name of rheotaxis, which,
he says, is a special kind of barotaxis. See also Adolphi, " Die Spermatozoon
der Saugethiere schwimmen gegen den Strom," Anat. Anz., vol. xxvi., 1905.
3 See Beck, " How Do the Spermatozoa enter the Uterus ? " Amer. Jour, of
Obstet., vol. viii., 1875.
4 See Williams, Obstetrics, New York, 1904.
5 Heape, "The Artificial Insemination of Mares," Veterinarian, 1898.
SPERM ATOGENES IS— INSEMINATION 181
action on the part of the latter organ. The os uteri, which is
situated above the ventral wall of the vagina, was observed to
dip down into the seminal fluid at the bottom of the vagina, and
then to be withdrawn again in conjunction with a peristaltic
contraction of the uterus. These movements were repeated at
intervals. Moreover, it was found that the sucking action
could be induced artificially by stimulating the erectile tissue of
the vulva. It is probable, however, that the spermatozoa,
after once entering the uterus, proceed to their destination un-
assisted, and that the direction of their movement is deter-
mined by the capacity they possess to respond to the stimuli
set up by opposing currents. Moreover, pregnancy has been
known to follow imperfect coition in Man, so that there can be
no doubt that under certain circumstances the spermatozoa are
capable of passing inward by their own unaided efforts.
INSEMINATION
The act of copulation results in the introduction of seminal
fluid through the generative aperture of the female. The
mechanism by which this is effected in the higher animals is
described in a future chapter, where the functions of the acces-
sory male organs are dealt with. The introduction of the fluid
into the female generative passages is known as insemination
(as distinguished from impregnation, which is the term used in
reference to the female when fertilisation takes place 1).
It is obvious that in those animals which ovulate spon-
taneously during the oestrus periods it should be possible to
induce pregnancy at such times by the artificial introduction of
spermatozoa into the vagina or into the uterus. That this
could actually be effected was probably first demonstrated by
Spallanzani,2 though there is evidence that the practice of
artificial insemination was not unknown to the Arabs many
centuries ago.3 The following is a description of Spallanzani's
1 That is to say, the animal is inseminated when the spermatozoa are
introduced, and it is impregnated when the ovum becomes fertilised by a
sperm. See Heape, " The Artificial Insemination of Mammals," Proc. Roy.
Soc., vol. Ixi., 1897.
- Spallanzani, Dissertations, vol. ii., London, 1784.
3 Gautier, Le Fecondation artificielle, &c., Paris, 1889.
182 THE PHYSIOLOGY OF REPRODUCTION
original experiment, as quoted from a contemporary English
translation :—
" I chose a bitch spaniel of moderate size which had before
had whelps. Suspecting, from certain appearances, that she
would soon be in heat, I confined her in an apartment, where
she continued a long time, as will be seen below. For greater
security, that she might never be let loose, I fed her myself, and
kept the key the whole time. On the thirteenth day she began
to show evident signs of being in heat ; the external parts of
generation were tumid, and a thin stream of blood flowed from
them. On the twenty- third day she seemed fit for the admission
of the male, and I attempted to fecundate her artificially in
the following manner. A young dog of the same breed furnished
me, by a spontaneous emission, with nineteen grains of seed,
which were immediately injected into the matrix, by means of
a small syringe introduced into the vagina. As the natural
heat of the seed of animals of warm blood may be a condition
necessary to render fecundation efficacious, I had taken care
to give the syringe the degree of heat which man and dogs are
found to possess, which is about 30° [or between 99° and 100°
Fahrenheit]. Two days after the injection, the bitch went off
her heat, and in twenty days her belly appeared swollen, which
induced me to set her at liberty on the twenty-sixth. Mean-
while the swelling of the belly increased ; and sixty-two days
after the injection of the seed, the bitch brought forth three
lively whelps, two male and one female, resembling in colour
and shape not the bitch only, but the dog also from which the
seed had been taken. Thus did I succeed in fecundating this
quadruped ; and I can truly say, that I never received greater
pleasure upon any occasion, since I first cultivated experi-
mental philosophy."
Spallanzani also records a similar experiment by Pierre
Rossi, in which a dog was impregnated by artificial means.
Considerable success has been obtained in recent years in ex-
periments on the artificial insemination of dogs. Gautier l refers to
a case in which pregnancy was induced by this means. Albrecht 2
1 Gautier, loc. cit.
2 Albrecht, " Kiinstliche Befruchtung," Wochenschr. f. Thierheilkunde und
Viehzucht, Jahrg. xxxix.
SPERMATOGENESIS— INSEMINATION 183
and Plonnis l have also described experiments in which they
successfully inseminated dogs by artificial methods (see p.
611). Heape 2 has recorded a series of experiments carried
out by Sir Everett Millais on the artificial insemination of
Basset hounds. The present writer has succeeded in inducing
pregnancy by this method in a Dandie Dinmont terrier. More-
over, there are numerous cases on record in which dogs have been
successfully inseminated artificially as a means of overcoming
certain forms of barrenness (see p. 611). The method adopted in
all these experiments was substantially the same as that em-
ployed by Spallanzani.
Artificial insemination is now also practised on mares, donkeys,
and cows, and usually with the object of remedying sterility.
In thoroughbred mares especially it has proved of great service,
having been the means of preserving for breeding purposes many
valuable animals which otherwise would have been discarded.3 .
Iwanoff 4 has described experiments in which pregnancy was
induced in rabbits and guinea-pigs by the artificial injection of
testicular fluid into the female generative passages. The same
investigator states that he induced hybridisation between
a male rat and a female mouse by artificially inseminating
the latter (see p. 611, Chapter XIV.).
He has shown, further, that the spermatozoa retain their
vitality sufficiently long to admit of their being employed
successfully in artificial insemination if they are kept in solutions
of various salts (sodium chloride, sodium carbonate, &c.) or in
serum instead of in the secretions of the accessory generative
glands. Hunter appears to have been the first to practise arti-
1 Plonnis, " Kiinstliche Befruchtung einer Hiinden," &c., Inaug. Dissert.,
Rostock, 1876. 2 Heape, loc. cit.
3 For references to particular experiments see Heape, " The Artificial
Insemination of Mares," Veterinarian, 1898 ; also a booklet published by
Huish (The Cause and Remedy of Sterility in Marcs, Cows, and Hitches,
London, 4th Edition, 1899), in which a large number of cases are described
in which artificial insemination was successfully carried out ; also Iwanoff,
" De la Fecondation Artificielle chez les Mammiferes," Arch, des Sciences
Biologiques, vol. xii., 1907. The last-mentioned paper contains an account
of a very large series of experiments on horses, cows, and sheep, with a
full description of the practical methods employed, and a very complete
account of the literature of the subject.
4 Iwanoff, "La Fonction des Ve"sicules seminales," &c., Jour, de Phys. et
de Path, gen., vol. ii., 1900.
184 THE PHYSIOLOGY OF REPRODUCTION
ficial insemination upon a woman (previously sterile),1 but it has
since been successfully adopted by various medical men, the
method being to inject the spermatozoa through the os into the
cavity of the uterus (see p. 609).
With those animals whose ova are normally fertilised outside
the body, artificial insemination is a still simpler process.
Spallanzani was the first to show that the eggs of various
species of Amphibia could be fertilised by the application of
fluid obtained from the testes or seminal vesicles of the male,
and that the frogs and newts which were generated by this
means in no way differed from those produced in nature.
Spallanzani was also successful in artificially fecundating the
eggs of the silk- worm moth.
Artificial impregnation of fish ova was first employed by
Jacobi,2 and the method which he adopted is practically the
same as that habitually practised at the present day for
stocking water-courses with fish.
The vitality of the spermatozoon appears to vary widely in
the different species of animals.
Leeuwenhoek,3 and subsequently Provost and Dumas,3
state that they found moving sperms in the internal genital
organs of female rabbits and dogs eight days after coition.
Bonnet 4 says that he observed motionless sperms, which,
therefore, were probably dead, but had not yet undergone
disintegration, in a bitch seventeen and a half days after coition.
In a series of experiments upon the longevity of the spermatozoon
in the rabbit, it was found that these cells can survive in the
vasa deferentia for at least ten days after the removal of the
testes, but that they die before the end of thirteen days.5
Spallanzani 6 cites the fact that a hen can lay fertilised eggs
twenty days after impregnation by a cock.
1 Home, " An Account of the Dissection of an Hermaphrodite Dog," Phil.
Trans., 1799.
2 See Gunther, Introduction to the Study of Fishes, Edinburgh, 1880.
3 See Waldeyer's article in Hert wig's Handbuch der L'ntivicklungslehre,
Jena, 1903.
4 Bonnet, "Giebt es bei Wirbelthieren Parthenogenesis," Merkel und
Bonnet's Ergebnisse d. Anat. u. Entwick, vol. ix., 1900.
5 Marshall and Jolly, "Contributions to the Physiology of Mammalian
Reproduction : The (Estrous Cycle in the Dog," Phil. Trans. B., vol. cxcviii.,
1905. 6 Spallanzani, loc. cit.
SPERMATOGENESIS— INSEMINATION 185
Strassmann l has recorded a case in which human spermatozoa
survived in the female generative passages for a week after
coition. Bossi 2 refers to a similar instance where the sperms
lived for over twelve days. In another rase described by
Diihrssen,3 living spermatozoa were found in a woman who
stated that coition had not been experienced for three and a
half weeks.
In many species of bats, as already mentioned, copulation
takes place in autumn and ovulation in the following spring,
so that the spermatozoa retain their vitality while stored up in
the uterus during the hibernating period. Sperms obtained
from the females at this time are dormant, but regain their
vitality on the application of warmth.4
The spermatozoa of some warm-blooded animals will stand
considerable variation in temperature and still retain their
vitality. Thus they have been known to live for many hours at
ordinary room temperature ; but, undoubtedly, ejected sperms
tend to survive longest if kept at body temperature. Heape 5
states that some seminal fluid of a dog was sent to him by post
in a glass tube, and on being examined eighteen hours after it
was obtained, fully half the spermatozoa were found to be
active and vigorous, while increased warmth stimulated to
activity those which showed signs of sluggishness but did not
revive the remainder.
In the experience of the writer, horses' spermatozoa die more
easily if exposed to cold. Chelchowski,6 in describing the
methods adopted in the artificial insemination of mares, lays
stress upon the necessity of keeping the seminal fluid warm,
and states that, if this is done, it is possible to keep the sperms
alive for twenty hours.
The case of bats, which has been referred to above, has a
parallel in certain cold-blooded animals. Thus, according to
1 Strassmann, Lehrbuch der gerichtlichen Mediz'n, 1895.
2 Bossi, " Etude Clinique et Expe"rimentale de 1'Epoque la plus favorable
k la Fecondcition de la Femme," Rivista di O7:stet. e Ginecol., 1891.
3 Diihrssen, " Lebendige Spermatozoen in der Tube," Centralll.f. Gynak.,
1893.
4 See Eimer and other references given on page 136.
5 Heape, loc. c:t.
6 Chelchowski, Die SterMtdt des Pferdes, Wien, 1894.
186 THE PHYSIOLOGY OF REPRODUCTION
Rollinat,1 in snakes belonging to the species Tropidonotus
viper inus the females are usually inseminated in the autumn,
whereas the eggs are not laid until the beginning of the following
summer. Also in the case of the spotted viviparous salamander
(Salamander maculosa) , after the birth of the young, which occurs
about the month of May, a new batch of ova pass into the
oviducts and are fertilised (prior to the commencement of the
sexual season) by spermatozoa which were introduced in the
July of the previous year, and thereafter stored in the uterus.2
It is obvious that in both these cases the spermatozoa retain
their vitality in the female for periods of many months.
In animals like the earthworm, in which the spermatozoa
are stored in special reservoirs known as spermathecse, it is
probable that they retain their vitality for long periods. Lang 3
has shown that the sperms may live for three years in the
vesiculse seminales of snails.
The extreme longevity possessed by the male cells of some
insects is still more remarkable. Von Siebold 4 states that
the spermatozoa of bees may survive for four or five years.
Moreover, queen ants have been known to lay fertile ova
thirteen years after the last intercourse with a male.
1 Rollinat, " Sur 1'Accouplement des Ophidiens a la Fin de 1'Ete et au
Commencement de 1'Automne," Bull. ZooL Soc. France, vol. xxiii., 1898.
2 Sedgwick, Student's Text-Book of Zoology, vol. ii., London, 1905.
3 Lang, " Uber Vorversuche zu Untersuchungen iiber die Varietaten-
bildungen von Helix hortensis Miiller and Helix nemoralis L.," Festschr. zum
siebz:gsten Geburtstage von Ernst Haeckel, Jena, 1904.
4 Von Siebold, " Fernere Beobachtungen iiber die Spermatozoon Wirbel-
loser Tiere," Mailer's Archiv, 1837.
CHAPTER VI
FERTILISATION
" Although it be a known thing subscribed by all, that the foetus
assumes its origin and birth from the male and female, and consequently
that the egge is produced by the cock and henne, and the chicken out of the
egge, yet neither the schools of physicians nor Aristotle's discerning brain
have disclosed the manner how the cock and its seed doth mint and coine the
chicken out of the egge." — HARVEY.
ALTHOUGH much progress has been effected, and many new
facts have been discovered, since Harvey wrote his famous dis-
sertation on " The Efficient Cause of the Chicken/' the actual
nature of the process whereby the ovum, after being discharged
from the ovary, is endowed with a new vitality through union
with a spermatozoon, is a problem the solution of which is still
far from complete.
In 1843 Martin Barry,1 as already mentioned, first observed
the union of the spermatozoon and ovum in the rabbit, and a
little later Newport 2 recorded its occurrence in the frog ; but it
was not until the last quarter of the nineteenth century that
the significance of the process was realised. It was largely
through the work of Hertwig, Strasburger, and van Beneden
that most biologists came to believe that the union of the nuclei
of the gametes was the essential act in the process of conjugation.
The more recent investigations of Boveri and others do not,
however, entirely support this conclusion.
As already described, the head of the spermatozoon represents
the nucleus, and contains the chromatin material. When the
sperm penetrates into the substance of the ovum the tail be-
comes absorbed, but the head remains as the male pronucleus.
The matured nucleus of the ovum, or female pronucleus (the
two polar bodies having been discharged), passes towards the
1 Barry, " Spermatozoa Observed within the Mammiferous Ovum," Phil.
Trans., 1843.
2 Newport, "On the Impregnation of the Ovum in the Amphibia," Phil.
Trans., 1851.
187
188 THE PHYSIOLOGY OF REPRODUCTION
centre of the cell, where it unites with the male pronucleus
which generally becomes somewhat enlarged. The middle-
piece of the spermatozoon also enters the egg, and, according to
Boveri,1 induces the formation of a centrosome, which, after the
completion of fertilisation, initiates the process of cell division.
i
.-.— I't.-"!.' • - •>..-'
FIG. 50. — Successive stages in the fertilisation of an ovum of Echinus
esculentus, showing the entrance of the spermatozoon. (From Bryce.)
Cytoplasmic filaments arrange themselves around the centro-
some in the form of a star, the sperm-aster, which accompanies
the male pronucleus, and afterwards comes to lie alongside of
1 Boveri, Zellen Studien IV., Ueber die Natur der Centrosomen, Jena,
1901. Jenkinson, " Observations on the Maturation and Fertilisation of the
Egg of the Axolotl," Qaar. Jour. Micr. Science, vol. xlviii., 1904, has re-
cently stated that the middle-piece of the spermatozoon, after forming the
centre of the sperm -sphere and sperm-aster, completely disappears, and that
the centrosome is formed from the sperm-nucleus at a later stage. (The
sperm-sphere is the clear area which forms in the ovum round the head and
middle-piece of the spermatozoon shortly after its entrance.)
FERTILISATION 189
the segmentation nucleus (as the nucleus formed by the union
of the two pronuclei is called). In the segmentation nucleus
the normal number of chromosomes characteristic of the specie^
is once more restored. The oosperm, or zygote, produced in this
way is the starting-point of a long series of cell divisions which
culminate in the formation of a new, completely developed
individual.
Jenkinson, who has carried out a series of experiments in-
tended to elucidate the physical processes occurring in fertilisa-
tion, draws the conclusion that the structures which appear in
the ovum are produced under the influence of the middle-piece
FIG. 51. — Three stages in the conjugation of male and female nucleus
in the fertilisation process of Echinus. (From Bryce.)
and centrosome. He supposes these bodies to possess the power
of withdrawing water from the cytoplasm, of swelling up and
dissolving in the water so absorbed, and then giving off radial
outgrowths which precipitate the proteins of the cell, and so
produce the fertilisation spindle. Jenkinson lays some stress
on the fact that a watery fluid collects in vacuoles in the centre
of the sperm-sphere of the axolotl, and regards the presence of
this fluid as evidence that the sperm introduces a hydroscopic
substance into the ovum. In confirmation of this the experi-
ments show that a hydroscopic particle is capable of giving rise
to an astral structure in a colloid solution.1
Boveri and others have proved experimentally that portions
of unfertilised Echinoderm ova, without egg nuclei, may develop
1 Jenkinson, loc. cit. Further references are given in this paper.
190 THE PHYSIOLOGY OF REPRODUCTION
normally after the addition of spermatozoa, while Driesch
has shown that if such ova are deprived of their envelopes
by shaking, and are then divided into fragments some of
which contain no nuclei, the latter are capable of being ferti-
lised a second time. It is clear, therefore, that in such cases
the union of nuclei is not essential for the development of the
ovum.1
In those ova which are surrounded by a membrane it is
probable that the fertilising spermatozoon bores its way through
at any point (Mammals and Am-
phibians). In other cases there is a
small aperture in the wall of the
ovum ; this is called the micropyle
(some Pisces and Insecta). Some
eggs, however, are naked, so that
the sperms may effect an entrance
anywhere on the surface (some
Echinoderms and Coelenterates), or
there may be funnel-shaped depres-
sions on the egg's periphery (certain
hydromedusse). 2
FIG. 52. — Fertilisation process In the majority of animals only
in bat's ovum. (After van one spermatozoon normally enters
the ovum, but in some (certain
p. b ,Polar bodies ; o. n., nucleus insects elasmobranch fishes, reptiles,
of ovum: s. n., nucleus of „ ,
spermatozoon. earthworm, lamprey, axolotl/ &c.),
several may effect an entrance.
The latter condition is called Polyspermy. Only one sperm-
nucleus conjugates with the ovum-nucleus ; the others as
a general rule undergo degeneration, but in a few cases
(elasmobranchs and reptiles) they are said to divide, forming
accessory nuclei whose ultimate fate is unknown. In those
animals in which only one sperm normally enters the egg,
pathological polyspermy may occasionally occur. In such cases
each sperm centrosome may give rise to a sperm-aster. The
1 For references to the original papers, which are somewhat numerous,
see Przibram, Embryogeny, English Translation, Cambridge, 1908.
2 Wilson, The Cell, &c., 2nd Edition, New York, 1900.
3 Jenkinson, loc. cit. Further references are given in this paper.
FERTILISATION 191
eggs which are fertilised in this way either do not divide at all
or go on dividing irregularly for a short time and then perish.1
It is supposed that the entrance of supernumerary sperrns_
is prevented normally either by some mechanical means, such
as the development of a membrane formed after the penetration
of the first sperm, or else by a change in the chemical constitu-
tion of the ovum, occurring as the immediate result of fertilisa-
tion.2 Thus, the brothers Hertwig 3 showed that in the case of
eggs the vitality of which had been reduced artificially (e.g. by
poisons), the vitelline membrane was formed so slowly after the
entrance of the first spermatozoon that others also were able to
make their way into the egg cytoplasm. On the other hand, the
ova of many animals in which no membrane is formed seem to
possess the capacity of resisting the entry of supernumerary
spermatozoa, and the same is apparently the case with those
ova which have a membrane before fertilisation, this membrane
being penetrated by only a single sperm. Loeb 4 has recently
suggested that polyspermy may be prevented by an alteration
in the surface tension of the egg after the entrance of the
spermatozoon.
In the Mammalia fertilisation takes place usually in the
upper part of the Fallopian tube.
THE HEREDITARY EFFECTS OF FERTILISATION
The attempts that have been made to interpret the nature
and essence of sexual reproduction may be ranged under two
heads, representing the two chief theories that have been
elaborated (with some modifications by their respective ad-
herents) to explain the observed phenomena.5 According to
1 Wilson, loc. cit.
2 Farmer, "On the Structural Constituents of the Nucleus," &c., Croonian
Lecture, Proc. Roy. Soc. B., vol. Ixxix., 1907.
3 Hertwig, O. and R., " Beitriige zur Kenntniss der Bildung, Befruchtung
und Teilung des tierischen Eies," Morph. Jahr., vols. ii. and iii., 1887.
4 Loeb, The Dynamics of Living Matter, New York, 1906.
5 For accounts of the various theories which have been put forward con-
cerning the nature of fertilisation, see Wilson, loc. cit., Geddes and Thomson,
The Evolution of Sex, 2nd Edition, London, 1901; Weismann, The Evolution
Theory, English Translation, London, 1904; and Lock, Variation, &c., London,
1906. Further references are given in these works.
192 THE PHYSIOLOGY OF REPRODUCTION
one hypothesis, conjugation of the gametes results in a re-
juvenescence which is essential for the perpetuation of the race
(see p. 212). According to the second theory, which is not
necessarily antagonistic to the first, gametic union is a source
of variation.1 The latter theory may now be briefly considered.
A full discussion of the hereditary effects of fertilisation is,
however, beyond the scope of the present work.
The doctrine that conjugation is a source of variation was
first promulgated at the beginning of the last century by
Treviranus. Subsequently Brooks 2 adopted the same idea, and
Weismann made it the basis of his famous theory of heredity.3
" Sexual reproduction is well known to consist in the fusion of
two contrasted reproductive cells, or perhaps even in the fusion
of their nuclei alone. These reproductive cells contain the
germinal material or germ-plasm, and this again, in its specific
molecular structure, is the bearer of the hereditary tendencies
of the organisms from which the reproductive cells originate.
Thus, in sexual reproduction, two hereditary tendencies are in
a sense intermingled. In this mingling I see the cause of the
hereditary individual characteristics ; and in the production of
these characters, the task of sexual reproduction. It has to
supply the material for the individual differences from which
selection produces new species/'
Weismann supposes the nuclear chromatin of the cell to
consist of a large number of self-propagating vital units which
he calls biophors. These biophors he believes to be grouped
1 A third theory, which has never obtained any great support among
biologists, suggests that the purpose of sexual reproduction may be to prevent
variation, and so preserve specific uniformity. According to this view the
sexual process, although continually creating new variations, is also con-
stantly obliterating them by tending to produce individuals possessing the
mean of their parents' characters. This theory, which is the converse of the
second theory referred to in the text, has received the support of the Hertwigs.
In this connection it may be remarked that variability is quite as great among
non-sexual parthenogenetic animals as among those which are reproduced
sexually. This fact is difficult to explain if we adopt the theory that the purpose
of gametic union is to induce variability. Moreover, Enriques (" La Con-
iugazione e il differenziamento sessuale negli Infusori," Arch. f. Protisten-
kunde, vol. ix., 1907), as a result of a series of experiments upon conjugation
in Infusoria, has adopted a similar view to that of the Hertwigs.
2 Brooks, The Law of Heredity, Baltimore, 1883.
3 Weismann, The Germ Plasm, English Translation, London, 1893.
FERTILISATION 193
together to form more complex units, named determinants,
which represent the separate parts of the organism. The de-
terminants are supposed to be aggregated together to com-
prise units of a still higher order, known as ids. These are
identified with the chroma tin granules. Every part of the
organism (or every character that it possesses) is believed to be
represented in an id. Moreover, Weismann assumes that the
ids vary slightly in related individuals, the differences in the ids
corresponding with the variations in the species. Lastly, the
ids are said to be arrayed in linear series so as to form idants.
Weismann identifies these with the chromosomes. It follows,
therefore, that each chromosome represents a particular group
of slightly differing germ-plasms. The purpose of variation, as
expressed in the terms of this theory, is to produce new com-
binations of heritable variations by the mixture of different
ids. And since the number of chromosomes, and consequently
the number of ids, is doubled as a result of the conjugating
process, the complexity of the chroma tin would become in-
definitely increased if there were no periodic reduction. But
this, according to Weismann, is provided against in the matura-
tion process of the gametes, when the quantity of chromatin
in the cells becomes reduced by one-half, as described in the
preceding chapters.
The reduced number of chromosomes is supposed to contain
all the primary constituents of each of the two parents. And
what is more, according to this theory, every gamete con-
tains ids which are derived, not only 'from both the parents,
but also from the ancestors, all the immediate ancestors being
represented.
Weismann's theory of the nature of fertilisation was ac-
cepted by many biologists as a working hypothesis, until the
disinterment of Mendel's discovery about ten years ago. The
confirmation of this discovery by numerous workers in different
fields has led to a revision of many of Weismann's conceptions.
The original experiments of Mendel 1 were upon hybridisation
1 Mendel, " Versuche iiber Pflanzen Hybriden," Verh. natur. f. Ver., in
Briinn, vol. iv., 1865. Reprinted in English in Mendel's Principles of
Heredity (Bateson), Cambridge, 1909. Mendel's work was rediscovered and
confirmed by de Vries, Correns, and Tchermak in 1900, and subsequently
N
194 THE PHYSIOLOGY OF REPRODUCTION
in peas, the two parent varieties initially selected differing from
each other in one particular character. The hybrids produced
by crossing were all similar superficially, and resembled one of
the parents in the character in question, which was therefore
called the dominant character, the other character being known
as recessive. When the hybrids were crossed among themselves,
approximately one half of the offspring were found to be
identical with their hybrid parents (dominant hybrids), one
quarter resembled one of the original varieties (the grandparent
with the dominant character), while the remaining quarter were
like the other pure variety (the grandparent with the recessive
character). Consequently the pure dominants and the dominant
hybrids resembled one another outwardly, but they differed in
their capacity to transmit the characteristics in question, since the
pure dominants alone were capable of always breeding true. The
recessives also invariably bred true. Mendel drew the conclusion
that in the hybrid the gametes (both male and female) were of
two kinds, which were respectively identical with the two kinds
represented by the gametes of the original pure varieties. The
differentiation of gametes carrying different characters is the
essential principle in Mendel's theory, the existence of dominant
and recessive characters, though often observable, being by no
means universal.
Another example, taken from the work of Bateson and
Punnett, will be sufficient to elucidate further the Mendelian
conception of game tic differentiation. Breeders of blue Anda-
lusian fowls have always recognised the practical impossibility
of obtaining a pure strain of this breed. However carefully
the birds are selected they invariably produce two sorts of
" wasters/' some being pure black, and some white with irre-
gular black marks or splashes. Bateson and Punnett were the
first to supply the explanation. They found that, on breeding
from a large number of blue Andalusian fowls, on an average
half of the offspring were blue like the parents, a quarter were
black, and a quarter were " splashed-white." They conse-
by Bateson and a large number of other workers. For a general account of the
Mendelian theory, and numerous references to the literature of the subject,
see Bateson, loc. cit. ; also Bateson, Saunders, Punnett, and Hurst, &c., in
Reports to the Evolution Committee of the Royal Society, Parts I., II., III.,
IV. and V., 1602, 1905, 1£06, and 1909.
FERTILISATION 195
quently drew the conclusion that the mechanism of inheritance
in the Andalusian fowl is comparable to what Mendel supposed
to exist in his hybrid peas. The gametes of the breed, according
to this hypothesis, instead of being all similar and carrying the
blue character (as one would suppose on Weismann's theory),
are of two different kinds, those of the one kind being bearers
of the black character, and those of the other being bearers of
the splashed-white character. Such gametes, uniting by chance
when the fowls mate together, give rise to three kinds of off-
spring, one black-white (becoming blue, actually, like the
parents), one black-black, and one white-white, these ap-
pearing (on an average) in the proportion of 2 : 1 : 1 according
to the law of probability. In this particular case of Mendelian
inheritance, neither of the two alternative parent characters
(i.e. neither black nor splashed-white) is dominant and neither
is recessive. Why black-bearing gametes uniting with white-
bearing gametes should give rise to blue individuals the
Mendelian theory does not attempt to explain.
The importance of Mendel's discovery lies in the fact that
it forms the basis of a theory whereby variability can be dis-
cussed in terms of the conjugating cells themselves, and not
merely in terms of the resulting zygotes. Moreover, it is a
theory which has been found to be applicable to a very wide
class of facts. There are reasons for supposing that sex is a
Mendelian phenomenon ; that is to say, that the ova and
spermatozoa are themselves sexual entities prior to conjugation
(see p. 633). It still remains to be proved, however, that the
principles underlying Mendel's theory are applicable to all
forms of inheritance.1
It has been mentioned that on Weismann's hypothesis
every gamete contains ids representing both its parents and all
its immediate ancestors. On the other hand, according to the
Mendelian theory, although all the essential characters of the
organism are represented in each germ cell, the Mendelian
characters, or allelomorphs as they are called, are each repre-
sented by paternal or maternal ids only, and not by both,
while the immediate ancestors have no representation at all.
1 Of. Darbishire, "Recent Advances in Animal Breeding," Royal Horti-
cultural Society's Report of the Conference on Genetics, London, 1907.
196 THE PHYSIOLOGY OF REPRODUCTION
It has been supposed that the chromatin granules (which
Weismann identified with the ids) are the carriers of the
Mendelian allelomorphs, and that when these fuse together
during the conjugation of the chromosomes which precedes
the process of reduction (see p. 130), there is an exchange of
allelomorphs between the chromosomes. If this interpretation
is correct, it is simply a matter of chance whether an allelo-
morph remains in the chromosome which originally contained
it, or becomes transferred to the other chromosome of the con-
jugating pair. And since each of the two chromosomes passes
into a different product of cell division, the allelomorphs
would become distributed in precisely the kind of way that the
Mendelian theory postulates.1
The Mendelian investigators have shown that by experimental
breeding it is apparently possible to superimpose certain char-
acters belonging originally to one kind of individual, upon
different characters belonging to another kind, thus creating
new combinations of characters. Thus it is claimed that by
starting with two individuals, each possessing two unit or
allelomorphic characters, which we may call A and X (associated
together in one individual) and B and Y (associated in the other),
it is possible in two generations to produce new individuals in
which the combinations are interchanged, A being associated
with Y, and B with X. It has been claimed also, that, in spite
of the new combinations, each of the original separate unit
characters can be preserved in a state of complete purity, and
without in any way affecting, or being affected by, the characters
upon which they have been superimposed. By resorting to such
methods, it has been thought possible to build up, little by
little, entirely fresh types of organisms, possessing new com-
binations of pure characters, which previously existed only in
different individuals.
It remains to be considered how far this conception of an
organism as an individual capable of description in terms of
unit characters (each of which can be transmitted pure) is in
harmony with modern physiological theory, or justified by
experimental investigation.
In the first place, it may be pointed out that the entire
1 Lock, loc. cit.
FERTILISATION 197
trend of physiological research in recent years has been to show
that the correlation that exists even between remote parts of
the body is often extraordinarily close, and that in all proba^
bility there is not an organ or structure that is not dependent
in its growth and activity upon chemical substances, elaborated
by other and sometimes distant parts of the body, and carried
thence in the circulating blood. Thus a change in the whole
metabolism, producing palpable modification in whole groups
of characters, may be induced experimentally in the individual,
by interfering with or removing one particular organ. This is
well shown in the various kinds of correlation existing between
the organs of internal secretion. Again, a change in the
environment may directly affect the metabolism, and so influence
all the characters of the body. To the physiologist, therefore,
a so-called unit character cannot readily be regarded as some-
thing represented by a substance located originally in a chromo-
some or chromomere. Such a view, as Verworn l remarks, is
" too morphologically conceived." It is more in keeping with
the physiological view of life to regard the characters of the
individual as manifestations of a particular kind of metabolism,
which is itself partly the outcome of environmental influences,
and partly the developmental result of the sort of metabolism
that existed in the germ cells from which the organism was
derived. According to this view, it is clear that the presence of
any one characteristic may exert an influence upon many, if not
upon all, the other characteristics, and that, even in heredity,
one cannot hope to alter any single organ or structure without
affecting, in some slight degree at any rate, all, or nearly all,
the other parts of the body. It may be argued, therefore, in
criticism of the Mendelian conception of unit characters, that it
takes little or no account of the metabolism of the organism as a
whole. Thus it has been shown that in the case of presence or
absence of hair pigment (which has been regarded as a simple
example of alternate characters, such as can be superimposed
experimentally upon other characters in the course of two
generations), there is a pronounced correlation between albinism
and other characteristics of the body, these characteristics
depending for their existence upon a common metabolism.
1 Verworn, loc. cit.
198 THE PHYSIOLOGY OF REPRODUCTION
Moreover, the difficulty experienced by Wood l in superimposing
the complete hornlessness of Suffolk sheep upon the white face
of the Dorset horns, is probably another example of the physio-
logical correlation subsisting between different, and apparently
unconnected, structures. Originally, this case was regarded as
one of simple superposition, and Bateson 2 describes the hornless
character as having been transmitted " pure," but subsequently
many of the so-called hornless sheep were found to have grown
scurs. The explanation which I tentatively suggest is, that the
character of pure hornlessness was somehow or other incompatible
with the pure white-faced character, these two characters being
ordinarily indications of two sorts of metabolism, in just the same
kind of way as the beef -producing quality and the milk-producing
quality seem to be to some extent incompatible in cattle.
I am inclined to go further, and to suspect that many of the
other Mendelian cases, when examined more critically, will show
that no one character can be superimposed upon another, in
experimental breeding, without altering, though perhaps only
very slightly, the character upon which it has been superimposed.
It is only when the amount of alteration is minimal that
the transmission of pure characters is apparent, according to
Mendelian expectation ; but experimental evidence has shown
that there are considerable numbers of such cases. It is a
legitimate field of work for the biometrical school of biology
to determine by statistical methods the extent to which varia-
tion occurs as a result of attempted superposition of characters
which in their " pure " state are physiologically incompatible.
Furthermore, a latent character may be regarded as one, the
outward manifestation of which is incompatible with the existing
kind of metabolism, but which is capable of reappearance as
soon as the conditions become favourable. But because it is
helpful to assume that latent characters are present in some
1 Wood, "The Inheritance of Horns and Face-Colour in Sheep," Jour.
Agric. Science, vol. iii., 1909.
2 Bateson, Mendel's Principles of Heredity, Cambridge, 1909. No doubt,
however, it is arguable that the scurs themselves represent unit char-
acters, and that if the scurs are of different kinds, these also represent
unit characters (which have hitherto somehow remained "latent"), and
that if they occur with different degrees of development, these again are
unit characters. And so on.
FERTILISATION 199
manner in the animal organisation, it is not legitimate to suppose
that they are definitely located in the nuclei of germ cells or in
any other definite parts or structures.1
Moreover, it should be remembered that there is no elJ?
perimental proof that the chromosomes of the gametes are
the physical basis of inheritance. The only definite evidence
in support of this supposition appears to be Bbveri's experiment,
in which he fertilised a non-nucleated ovum of one species of
sea-urchin with the spermatozoon of another species.2 The
resulting pluteus or larva was purely paternal in its characters.
Boveri concluded, therefore, that this result was due to the
introduced nucleus, the maternal cytoplasm having no deter-
mining effect upon the offspring, but merely supplying the
material upon which the sperm operated.3 Seeliger,4 Morgan,5
and others have objected to Boveri's conclusion on the ground
that larvae arising from cross-fertilisation show an unusually
wide range of variation. Moreover, Godlewsky 6 has recently
carried out an experiment in which he fertilised a non-nucleated
portion of a sea-urchin's egg with the spermatozoon of a crinoid,
and obtained, as a result, a larva of the maternal type. This
experiment seems to nullify Boveri's conclusion.
Hickson has remarked that if it be true that the chromosomes
are the sole carriers of heredity it seems to be necessary to be-
lieve in the individuality of the chromosomes ; that is to say,
1 The attempt to locate latent characters of organisms in particular
parts of the germ cells should perhaps be regarded as a survival from
a time when all kinds of qualities, abstract or otherwise, were supposed
to reside in definitely restricted positions. " Compare Phenology. The
centres in the nervous system are not comparable, since these are to be
regarded as parts of mechanisms for controlling different functions. The
centres preside over the respective functions, but the functions themselves
are not located in the centres."
2 Boveri, " Ein Geschlechtlich erzeugter Organismus ohne Miitterliche
Eigenschaften," S. B. d. Ges. f. Morph. u. Phys., Miinchen, vol. v., 1889.
3 The nuclei of such larvse have been shown to possess only half the
normal number of chromosomes ; see Morgan, " The Fertilisation of Non-
nucleated Fragments of Echinoderm Eggs," Arch. f. Entwick.-Mechanik,
vol. ii., 1895.
4 Seeliger, " Giebt es Geschlechtlicherzeugte Organismen ohne Miitter-
liche Eigenschaften? " Arch. f. Entwick.-Mechanik, vol. i., 1894.
5 Morgan, loc. cit. See also Wilson, loc. cit.
6 Godlewsky, " Untersuchungen iiber die Bastardierung der Echiniden
und Crinoiden-Familie," Arch.f. Entwick.-Mechanik, vol. xx., 1906.
200 THE PHYSIOLOGY OF REPRODUCTION
that the chromosomes seen at the poles of the spindle at the
termination of mitosis are individually identical with those
seen at the equator of the spindle at the next mitosis. He
points out, further, that there is distinct evidence that this is
not the case in certain Protozoa and Coelenterata. Again,
Hickson has called attention to the long duration of the period
of conjugation in Infusoria (Heterokaryota), remarking that
this is difficult to explain if we accept the view that the cyto-
plasm of the conjugating cells is not concerned with the trans-
mission of hereditary characters.1
Verworn, in the criticism referred to above, has objected
on more general but scarcely less substantial grounds to the
doctrine that the hereditary transmission of parental char-
acteristics is mediated by the transference of nuclear substance
only. ' The physiological mode of thought will hardly be
able to adapt itself to the idea of a single hereditary
substance, which is localised somewhere in the cell, and
transferred in reproduction. A substance that is to convey
the characteristics of a cell to its descendants, before all else
must be capable of life, i.e. must have a metabolism, and this is
impossible without a connection with other substances necessary
to cell-metabolism, i.e. without the integrity of all essential
cell-constituents. The designation of a single cell-constituent
as the specially differentiated bearer of heredity is wholly un-
justified ; the cell protoplasm is of exactly the same value in
this respect as the nucleus, and we must constantly return to
the fact that in all living nature no instance is known in which
a complete cell possessing nucleus and protoplasm does not
always mediate hereditary transmission. The character of
every cell is determined by its peculiar metabolism. Hence, if
the peculiarities of a cell are to be transmitted, its characteristic
metabolism must be transmitted ; this is only conceivable when
nuclear substance and protoplasm, with their metabolic relations,
are transferred to the daughter-cells. This is true of the sexual
reproduction of the higher animals, as well as of the asexual
1 Hickson, " The Physical Basis of Inheritance," British Assoc. Reports,
Leicester Meeting, 1907, and Trans. Manchester Micr. Soc., 1907. See also
Fick, " Vererbungsfragen Reduktions und Chromosomen hypothesen Bastard-
regeln," Merkel und Bonnet's Ergeb.f. Anat. u. Phys., vol. xvi., 1906.
FERTILISATION 201
reproduction of unicellular organisms ; in the former, however,
the metabolism of one cell, the spermatozoon, is by the process
of fertilisation combined with that of another cell, the ovum,
into a single resultant, the metabolism of the offspring that
arises from the fertilised ovum ; the offspring hence possesses
the characters of the two parents/' l
In view of the considerations set forth above it must be
admitted that the question as to the respective parts played
by the nucleus and the cytoplasm in hereditary transmission
remains as yet unsolved.
TELEGONY
It used to be supposed that the spermatozoa of an animal
on being introduced into a female of the same kind, besides
fertilising the ripe ova and producing young, were capable of
exercising a permanent influence over the mother, and so trans-
mitting certain of their characters, not only to their own
immediate offspring, but to the future offspring of the mother
by another sire. This phenomenon,2 in which many practical
breeders still believe, was called Telegony or Infection, and the
female was said to be " infected " by the previous sire.
The classical example, and one in which Darwin 3 himself
believed, of the supposed influence of a previous sire upon the
future offspring, is the case of Lord Morton's quagga, which
was stated to have infected an Arab mare, so that she subse-
quently produced two striped colts by a black Arab horse. In
recent years Ewart 4 has repeated the experiment, employing a
1 Verworn, loc. cit. Cf. Farmer (loc. c ?'£.), who regards the chromo-
somes of the nucleus as representing primordia, which are responsible
for the appearance of the hereditary characters, but need to be supple-
mented by specific exciting substances which determine what particular
potential character shall actually develop.
2 The phenomenon was explained by supposing that the young, while
still in utero, in some way affected the mother, and this influence was
further transmitted to the subsequent offspring. It will be seen that this
explanation assumes the possibility of the inheritance of acquired characters
of which there is little or no evidence. For recent reviews of this ques-
tion see Morgan, Experimental Zoology, New York, 1907 ; and Thomson,
Heredity, London, 1907.
3 Darwin, The Variation of Animals and Plants under Domestication,
Popular Edition, vol. i., London, 1905.
4 Ewart, The Penycuik Experiments, London, 1899.
202 THE PHYSIOLOGY OF REPRODUCTION
BurchelFs zebra and a number of different mares. These ex-
periments were supplemented by others in which animals of
various kinds were used. As a result of his investigations he
has come to the conclusion that there is no evidence for the
existence of Telegony. A microscopic examination of the
structure of the hairs of the subsequent foals bred by Pro-
fessor Ewart provided further negative evidence.1 Minot,2
also, in a series of experiments upon guinea-pigs, found no
indication of any telegonic influence. Moreover, Karl Pearson,3
as a result of an extensive statistical inquiry, was unable to
discover any evidence of telegony in Man.
ON GAMETIC SELECTION AND THE CONDITIONS FAVOURABLE FOR
THE OCCURRENCE OF FERTILISATION
It is a well-known fact in biology that, as a general rule,
conjugation occurs most readily between gametes belonging to
the same kind of organism. There are innumerable cases,
however, in which the spermatozoa of one species are capable
of fertilising the ova of another, and so initiating development.
The resulting embryo in such cases may grow into a mature
hybrid offspring which is not infrequently sterile (a fact which
will be referred to again later), or, on the other hand, owing to
some mutual incompatibility in the respective modes of growth
inherited from the two parent forms, the embryo may survive
for a short time and then perish.
Cross-fertilisation can usually be induced most easily among
closely related species or among varieties belonging to the same
species. Thus, the different varieties of the frog, Rana fusca,
intercross as readily with one another as each variety fertilises
its own ova. On the other hand, the gametes of two species as
widely separate as the frog, Rana fusca, and the salamander,
Triton alpestris, have been known to conjugate, but the
fertilised eggs so produced divided irregularly and consequently
1 Marshall, "On Hair in the Equidae," Proc. Roy. Soc. Edin., vol. xxiii.,
1901.
2 Minot, "An Experiment with Telegony," British Assoc. Reports, Cam-
bridge Meeting, 1904.
3 Pearson, The Grammar of Science, 2nd Edition, London, 1900.
FERTILISATION 203
failed to develop.1 In some cases (e.g. the two species of frogs,
R. fusca and R. arvalis) cross-fertilisation can take place in one
direction, but not in the reverse. Pfliiger explained this result
by supposing it to be due to peculiarities in the shape or structure
of the spermatozoa, those which have the thinnest or most
pointed heads being described as more successful in inducing
cross-fertilisation than those with large stout heads.2 This
explanation, while seeming to account for certain individual
instances, cannot be applied to all cases of cross-sterility.
Bataillon 3 has described experiments in which he fertilised
the eggs of Pelodytes and Bufo with the spermatozoa of Triton
alpestris, and obtained some degree of success, for the eggs in
each case underwent an irregular segmentation before they
perished. The spermatozoa underwent degeneration after con-
jugating, so that the chroma tin of the fertilised ova was derived
entirely from the female pronucleus. The experiments, there-
fore, afford additional proof that spermatozoa in conjugating
with ova perform a function altogether apart from amphimixis
(or the introduction of fresh chromatin substance as a source
of variation), and that this function is the initiation of de-
velopment.
Among, the Mammalia, as is well known, cross-fertilisation
between nearly allied species commonly occurs. The resulting
hybrid may be either sterile (e.g. the mule) or fertile (e.g. the
hybrid offspring of the bull and American bison). There is
no evidence that more widely separated species of Mammals
can be induced to have hybrid offspring. Spallanzani,4 by
artificially inseminating an oestrous bitch with the spermatozoa
of a cat, attempted such an experiment, but without a positive
result.
A number of investigators have effected cross-fertilisation
between various kinds of Echinoderms. Vernon,5 who experi-
1 Pfltiger, "Die Bastardzeugung bei den Batrachiern," Pfluyer 's Arch.,
vol. xxix., 1882.
2 Pfliiger and Smith, " Untersuchungen iiber Bastardierung der Anuren
Batrachier," &c., Pfliig<r's Archiv, vol. xxxii., 1883.
:{ Bataillon, " Impregnation et Fecondation," G. R. de VAcad. des Sciences,
vol. cxlii., 1906.
* Spallanzani, Dissertations, English Translation, vol. ii., London, 1784.
5 Vernon, "The Eelation between the Hybrid and Parent Forms of
Echinoid Larvae," Phil. Trans. B., vol. cxc., 1898.
204 THE PHYSIOLOGY OF REPRODUCTION
merited with forty-nine different combinations, obtained results
which were more or less successful in thirty-seven. In some of
these, however, development did not proceed beyond the
blastula stage. Vernon attempted to show that the capacity
of the animal to transmit its characters to its hybrid offspring
depended upon the condition of ripeness or staleness of its
gametes at the time of fertilisation. Thus, the spermatozoa of
the sea-urchin, Strongylocenlrotus, were supposed to grow more
and more " prepotent " as they became more and more mature.
Doncaster,1 however, has described further experiments which
seem to indicate that the variation in the form of the hybrids
obtained by Vernon was really due to differences in the
temperature of the water.
Loeb 2 discovered that cross-fertilisation of the eggs of
Strongylocentrotus by the spermatozoa of various species
of starfish could be effected by adding sodium carbonate or
sodium hydroxide to the sea- water in just sufficient quantity to
render it slightly alkaline. Under these conditions as many as
fifty per cent, of the Strongylocentrotus eggs could be fertilised
by Asterias spermatozoa, whereas in normal sea-water cross-
fertilisation between these two Echinoderms only occurs very
exceptionally. What the nature of the change is whereby the
alkaline sea-water enables the sperm to fertilise the ova does
not appear to be known. It has been observed that the addition
of the alkali increases the motive-power of the sperms, but the
same result is brought about by bicarbonate of sodium, without
augmenting their capacity to cross-fertilise. Loeb suggests that
the entrance of the spermatozoon into the interior of the egg-
1 Doncaster, ''Experiments in Hybridisation," Phil. Trans. B., vol. cxcvi.,
1903. MacBride ("Some Points in the Development of Ophiothrix fragilis"
Proc. Roy. Soc. B., vol. Ixxix., 1907) has recently shown that the immature
(ovarian) ova of the Ophiuroid, Ophiothrix, may be fertilised, but that the
subsequent development is abnormal, segmentation resulting in a morula
instead of a blastula, while at the stage at which the archenteron is formed,
there is a tongue of cells projecting into its lumen. It appears, therefore, that
the stage of maturity at which ova are fertilised may affect their embryonic
development if not their hereditary characteristics.
2 Loeb, " Ueber die Befruchtung von Seeigeleiern durch Seesternsamen,"
Pfluger's Archiv, vol. xcix., 1903. "Weitere Versuche iiber heterogene
Hybridisation bei Echinodermen," Pfliiger's Archiv, vol. civ., 1904. See
also translation of the latter, as well as other papers, in the University of
California Publications, Physiology, vols. i. and ii., 1902-4.
FERTILISATION 205
protoplasm may be due to surface-tension forces, and that the
conditions for this process may depend upon the surface tension
between the spermatozoon and the sea-water becoming greater
than the sum of the surface tensions between the sea-water and
the egg, and the spermatozoon and the egg. Loeb remarks,
further, that the fertilisation of Strongylocentrotus eggs by
sperms of the same species can best be accomplished in normal
sea-water, and with this observation he associates the fact that
the mobility of the Strongylocentrotus sperms is diminished by
the alkaline water.1
While suggesting that restrictions to the power of cross-
fertilisation may be due to differences in surface tension, Loeb
admits that the evidence seems to show that the capacity to
conjugate is to some extent at least specific. Attempts were
made to fertilise the eggs of sea-urchins with the spermatozoa of
Annelids and Molluscs, but these experiments were without
success. Very recently, however, Kupelweiser 2 reports that
he has been successful in fertilising Strongylocentrotus ova
with the spermatozoa of the mussel (Mytilus), and that the
products developed into gastrulse.
Dr. A. T. Masterman tells me that, in certain cases, hybridisa-
tion among fishes may be induced more readily in the absence
of opportunity for normal fertilisation, that is to say, for fertilisa-
tion of ova by spermatozoa of the same species. If such ova
are present, the spermatozoa tend to conjugate with them rather
than with ova belonging to a different but closely allied species.
It would appear, therefore, that the spermatozoa exhibit an
elective affinity for ova belonging to the same species as them-
selves. This has been shown especially in hybridisation experi-
ments between brill and turbot.3
That assortative mating amongst gametes occurs generally as
the result of a preferential tendency possessed by them towards
conjugating with other gametes bearing similar characters to
1 Loeb, The Dynamics of Living Matter, New York, 1906.
2 Kupelweiser, "Versuche liber Entwickelungserregung und Membran-
bilrlung bei Seeigeleiern durch Mollusksperma," Biol. Centrabl, vol. xxvi.,
1906.
3 M'Intosh and Masterman, Life History and Development of the Food
Fishes, and articles in the Reports of the Scottish Fishery Boards, 9th Rep.,
Pt. III., 10th Rep., Pt. III., and 13th Rep., Pt. III.
206 THE PHYSIOLOGY OF REPRODUCTION
their own, and that the comparative scarcity of hybrids in a
state of nature is very largely the result of this selective action,
are facts with which many of the older naturalists were familiar.
With reference to the various species of plants belonging to the
family Composite, Darwin wrote as follows :—
' There can be no doubt that if the pollen of all these species
could be simultaneously or successively placed on the stigma of
any one species, this would elect with unerring certainty its own
pollen. This elective capacity is all the more wonderful as it
must have been acquired since the many species of this great
group of plants branched off from a common progenitor/'
Romanes,1 who quotes this passage, remarks that " Darwin is
here speaking of ' elective affinity ' in its fully developed form,
as absolute cross-sterility between fully differentiated species.
But we meet with all lower degrees of cross-infertility — sometimes
between ' incipient species/ or permanent varieties, and at
other times between closely allied species. It is then known as
' prepotency ' 2 of the pollen belonging to the same variety or
species over the pollen of another variety or species, when both
sets of pollen are applied to the same stigma. Although in the
absence of the prepotent pollen the less potent will fertilise the
seed, yet, such is the appetency for the more appropriate pollen,
that even if this be applied to the stigma some considerable
time after the other, it will outstrip or overcome the other in
fertilising the ovules, and therefore produce the same result on
the next generation as if it had been applied to the mother
plant without any admixture of the less potent pollen, although
in some cases such incipient degrees of cross-infertility are
further shown by the number or quality of the seeds being
fewer or inferior/'
It would appear, however, that when the aggregate vitality
1 Romanes, Darwin and After Darwin, vol. iii., London, 1897. See also
Darwin, Animals and Plants, London, 1875, and Cross- and Self-Fertilisation
in Plants, London, 1876.
2 The term "Prepotency" is here used in a different sense to that in
which it is usually employed by zoologists, according to whom it means the
greater capacity of one parent, as compared with the other, to transmit its
characters to its offspring ; thus, instead of both parents transmitting their
characters equally, one may be "prepotent" over the other. (Of. the
Mendelian term "dominant," which has a more precise signification; see
p. 194.)
FERTILISATION 207
of the ova and spermatozoa is reduced below a certain point,
assortative mating as a result of affinity between gametes bearing
similar characters no longer occurs. It thus happens that a__
reduction of vitality is frequently correlated with an increased
tendency towards cross-fertilisation, which, on this view, is a
source of renewal of vitality. This theory was adopted to ex-
plain certain phenomena of cross-fertilisation occurring among
plants, by Fritz Miiller, who wrote as follows :—
" Every plant requires for the production of the strongest
possible and most prolific progeny, a certain amount of difference
between male and female elements which unite. Fertility is
diminished as well when this degree is too low (in relatives too
closely allied) as when it is too high (in those too little related)/'
And, further, " species which are wholly sterile with pollen of
the same stock, and even with pollen of nearly allied stocks,
will generally be fertilised very readily by the pollen of another
species. The self-sterile species of the genus Abutilon, which
are, on the other hand, so much inclined to hybridisation,
afford a good example of this theory, which appears to be con-
firmed also by Lobelia, Passiflora, and Oncidium." l
Castle 2 found that the eggs of the hermaphrodite Ascidian,
Cionaintestinalis, could not, as a rule, be fertilised by spermatozoa
derived from the same individual, while they could be fertilised
readily with the spermatozoa of another individual. This rule,
however, was not without exceptions, for in some cases as many
as fifty per cent, of the eggs of one dona could be fertilised with
sperms of the same individual, although this was very unusual.
Morgan, who confirmed Castled observations, states that the
failure to conjugate is due to the inability of the sperms to
enter the eggs. If the sperm succeeds in entering, as in the
exceptional cases, the fertilised egg develops normally. Morgan
found, further, that if the sperms are stimulated to greater
activity by alcohol, ether, ammonia, or certain salt solutions,
self-fertilisation may in some cases be induced. In another
Ascidian, Cynthia partita, Morgan observed that self-fertilisa-
1 Miiller, " Investigations respecting the Fertilisation of Abutilon"
English Translation in American Naturalist, vol. viii., 1874.
2 Castle, " The Early Embryology of dona intestinalis" Bull. Mus. Comp.
Zool., vol. xxvii., 1896.
208 THE PHYSIOLOGY OF REPRODUCTION
tion frequently occurs, but that the eggs in this species also are
most usually fertilised by spermatozoa from another individual.1
It is well known that the fertility of animals which are much
in-bred is often reduced, but this is by no means invariably the
case.2 Thoroughbred horses are notoriously in-bred, and it is
interesting to note that one of the earlier reports of the Royal
Commission on Horse-breeding states that no less that forty per
cent, of the thoroughbred mares in this country fail to have foals
each year. This relatively large amount of sterility is probably
due to a variety of causes, and not entirely to the results of
in-breeding.
Low 3 has recorded an experiment on the effect of in-breeding
in fox-hounds. The particular strain is described as having
perished completely. Low states also that similar experiments
have been performed upon pigs, and, as a consequence, the
litters became diminished in size and frequency, while difficulty
was often experienced in rearing those which were produced.
Von Guaita,4 and Bos,5 in describing the effects of in-
breeding in mice and rats respectively, have recorded a steady
decrease of fertility in successive generations.
Castle and his collaborators,6 as a result of an investigation
upon the same question in the pumice-fly (Drosophila am-
pelophila), have come to the conclusion that in-breeding tends
to reduce the fertility to a slight extent, whereas cross-breeding
has a contrary effect.
The diminished fertility of in-bred animals may be due
partly to a decrease in the supply of mature ova correlated with
1 Morgan, "Self-Fertilisation induced by Artificial Means," Jour, of
Exper. ZooL, vol. i., 1904. " Some Further Experiments on Self -Fertilisation
in dona," Btol. Bull., vol. viii., 1905.
2 The results of in-breeding are discussed at some length by Darwin,
Variation of Animals and Plants, vol. ii., Popular Edition, London, 1905.
For a recent review of the subject see Morgan, Experimental Zoology,
New York, 1907.
3 Low, The Domesticated Animals of Great Britain, London, 1845.
4 Von Guaita, " Versuche mit Kreuzungen von verschiedenen Rassen der
Hausmaus," Ber. d. Naturf. Gesell., Freiburg, vol. x., 1898.
5 Bos, " Untersuchungen ueber die Folgen der Zucht in engster Blutver-
wandtschaft," Biol. CentralbL, vol. xiv., 1894.
6 Castle, Carpenter, Clark, Mast, and Barrows, " The Effects of In-breeding,
&c., upon the Fertility and Variability of Dros&phila" Proc. Amer. Acad. of
Arts and Sciences, vol. xli., 1906.
FERTILISATION 209
a general want of vigour. It seems probable, however, that it
also results from failure on the part of the gametes to conju-
gate, since the productiveness of in-bred animals can often be
increased by cross-breeding with other varieties. (See p. 601.J
Heape 1 states that Dorset Horn sheep, when served by
rams of their own breed, show a greater tendency towards
barrenness than when served by Hampshire Down rams. It
is possible that what in this case appears to be barrenness is
in reality very early abortion, the in-bred embryos tending
to die at an early stage and to be absorbed in utero, thus
escaping observation. It seems not unlikely, however, that, in
the absence of cross-breeding, there is sometimes an insufficiency
of vitality at the very outset, the elective affinity of the gametes
being too feeble to induce conjugation.
Some years ago the writer carried out an experiment upon
a bitch belonging to the Dandie Dinmont variety, which is
known to be very in-bred. Seminal fluid was obtained from a
pure-bred Dandie Dinmont dog, and also from an obviously
mongrel terrier of unknown ancestry. The semen from the two
dogs was examined microscopically, and in each case was found
to be rich in sperms, which so far as seen were all moving and
in a vigorous condition. Approximately equal quantities of
each sample of semen were then mixed together in a glass tube.
After a further examination of the mixture, when it was
observed that all the sperms were still active, the fluid was
injected into a pure-bred Dandie Dinmont bitch, which was
distantly related to the Dandie Dinmont dog. Previously to
the experiment the bitch had been kept apart from other dogs,
and this restriction was continued so long as she showed signs
of oestrus. Fifty-nine days after the injection the bitch littered
four pups, which closely resembled one another. Of these one
died early, but the other three grew into mongrels which some-
what resembled the terrier sire, so that there can be little doubt
that all four pups were mongrels. No stress should be laid
upon the result of a single experiment ; but the evidence, such
as it was, was indicative of a selective tendency, consequent
upon a reduced vitality, on the part of the ova of the in-bred
1 Heape, " Abortion, Barrenness, and Fertility in Sheep," Jour, Royal
Agric. Soc., vol. x., 1899.
O
210 THE PHYSIOLOGY OF REPRODUCTION
animal to conjugate with dissimilar rather than with related
spermatozoa.
Professor Ewart has informed the writer of a case in which
a Dandie Dinmont bitch in his possession copulated with a
dog belonging to the same breed, and two days subsequently
had intercourse with a Scotch terrier. In due time the bitch
littered three pups, and of these only one was a pure-bred
Dandie Dinmont, while the other two were half-bred Scotch
terriers, in spite of the fact that the Dandie Dinmont dog
copulated two days earlier than the Scotch terrier. This case
may be regarded as to some extent confirmatory of the experi-
ment described above.1
Doncaster,2 in describing his experiments on Echinoid
hybridisation, states " that cross-fertilisation is assisted by
conditions which tend to reduce the vitality of the eggs." This
artificial reduction of vitality could be accomplished either by
warming the eggs, or by shaking them, or by keeping them for
several hours, or by placing them for from one to two hours in
diluted sea-water, the last method being the most uniformly
conducive to the occurrence of cross-fertilisation. There is
some evidence, therefore, that a reduction of vigour among the
gametes, whether occurring naturally as a consequence of in-
breeding or produced artificially as in Doncaster's experi-
ments, may lead to a similar result, since both conditions
may bring about an increased tendency towards the union of
dissimilar gametes. On another view, the tendency towards
1 Seeing that an assortative mating of gametes can probably occur
between the ova of one individual and the spermatozoa derived from different
individuals, whether as a result of gametic similarity or reduction of vitality,
it is not improbable that gametic selection also sometimes takes place when
various gametes of a single individual are bearers of different characters,
in the manner postulated by the Mendelian theory. Such a preferential
mating, if it exists, would of course obscure the evidence of that very
gametic segregation, the probable existence of which, in other cases, is in-
ferred from the numerical proportions in which the different sorts of zygotes
or offspring are produced ; for if there is an assortative mating among the
gametes, it is obvious that the offspring would no longer be produced in
definite Mendelian proportions, since these depend upon the chance unions of
gametes. According to this view, prepotency may perhaps be interpreted
as the tendency of the gametes of an individual to conjugate with other
gametes bearing similar heieditary characters.
8 Doncaster, loc. cit.
FERTILISATION
cross-fertilisation in Doncaster's experiments may be looked
upon as evidence of a diminished power of resistance, on the
part of the ova, to the entrance of foreign spermatozoa, conse^
quent upon a reduced vitality in the ova.1
Further evidence upon this question is afforded by studying
the Protozoa. (See also pp. 601-604.)
CONJUGATION IN THE PROTOZOA
The phenomenon of conjugation in the Protozoa possesses
a special interest, inasmuch as it is undoubtedly the forerunner
of fertilisation in the Metazoa. It is clear, therefore, that a
complete understanding of the changes which attend the former
process cannot fail to throw great light on the nature and signi-
ficance of gametic union in multicellular organisms.
In the different groups of Protozoa all gradations are to be
found between conjugation in the general sense (i.e., the union,
either temporary or permanent, of two similar unicellular
organisms), and a process identical with metazoan fertilisation.
Thus, in the peritrichous Ciliata there is a pronounced sex
differentiation in the size and activity of the gametes, which
clearly correspond to ova and spermatozoa. Even the matura-
tion phenomena, which play so important a part in the develop-
mental history of the metazoan gametes, are represented in
some sort by comparable processes which have been observed
in certain Protozoa.2 There can be no doubt, therefore, as to
the essential similarity of conjugation in unicellular organisms
and fertilisation in multicellular ones.
Raymond Pearl,3 as a result of a biometrical study of the
process of conjugation in Pammceiium caudatum, has arrived
1 It may be mentioned also that Loeb has shown that, whereas mature
starfish eggs soon die if fertilisation is prevented, eggs in which maturation
is artificially hindered through lack of oxygen or the addition of an acid to
the sea-water, remain alive much longer than when allowed to become mature.
(Loeb, "Maturation, Natural Death, and the Prolongation of the Life of
Unfertilised Starfish Eggs," £c., Biol. Bull., vol. iii., 1902.) It would appear
therefore that the mature eggs have suffered a loss of vitality which
ordinarily can only be increased by the act of fertilisation.
2 See Enriques, loc. cit.
3 Pearl, " A Biometrical Study of Conjugation in Paramcecium," B-ome-
treka, vol. v., 1907.
THE PHYSIOLOGY OF REPRODUCTION
at the conclusion that in this protozoon there is a definite
tendency for like individuals to mate with like, since there is a
considerable degree of homogamic correlation both between the
lengths of the conjugant pairs and also between their breadths.
Evidence is presented to show that the homogamic correlation
arises through1 the necessity for the anterior ends and mouths
of the two individuals to " fit " reasonably well in the act of
successful conjugation. If this is so, the necessity for assortative
mating in Pammcecium is purely mechanical, and the principle
involved is not of general application to other game tic organisms.
Pearl states, also, that there is no evidence that conjugation
tends to produce increased variability in ex-con jugants. On
the contrary, there are indications that conjugation tends to
restrict the existing variability induced by environmental in-
fluences ; or, in other words, to preserve a relative stability of
type. This conclusion is antagonistic to Weismann's hypothesis
referred to above. (See footnote l, p. 192.)
As already mentioned, the reproductive processes in the
Protozoa, like those in the Metazoa, tend to run in cycles, each
cycle beginning and ending with an act of conjugation.
Maupas' observations showed that in various genera of In-
fusoria (Paramcecium, Stylonychia, &c.) a long period, during
which the animals multiply by simple cell division, is succeeded
by a period when conjugation is of very common occurrence.
This marks the commencement of a new cycle, being physio-
logically comparable to the period of sexual maturity in multi-
cellular organisms. If conjugation were prevented from occur-
ring, the individuals gradually ceased to divide and underwent
changes which invariably led to death. As a result of these
experiments, Maupas arrived at the conclusion that the purpose
of conjugation is to counteract the tendency towards senile
degeneration, and to bring about a rejuvenescence or renewal
of vitality.1
Maupas' observations have been confirmed by Joukowsky 2
1 Maupas, " Recherches experimentales sur la Multiplication des Infusories
CilieV' Arch, de Zool. Exp. et Gen., vol. vi., 1888. " Le Kegennissement
Karyogamique chez les Cilia's," Arch, de Zool. Exp. et Gen., vol. vii., 1889.
2 Joukowsky, " Beitrage zur Frage nach den Bedingungen der Ver-
mehrung und des Eintrittes der Konjugation bei den Ciliaten," Verh.
Nat. Med. Ver. , Heidelberg, vol. xxvi., 1898.
FERTILISATION
and Simpson,1 and more particularly by Calkins.2 The last
investigator found, further, that the periodic seasons of " de-
pression " or loss of vitality which invariably occurred _if _
conjugation were prevented, and which normally resulted in
the cessation of cell division and ultimately in death, could
be tided over and the race carried through further cycles of
activity by having recourse to artificial stimuli in the medium
surrounding the culture. In a series of experiments, which
Calkins conducted for twenty-three months with a single race of
Paramoecium, it was found that periodic reductions of vitality
occurred at intervals of about six months. At such times the
race under cultivation would have died out entirely had it not
been for the application of stimuli in the form of extracts of
various food substances (beef, pancreas, brain, &c.). With the
assistance of these restoratives, on three separate occasions, this
particular race of Paramcecium was carried through four cycles
of activity and 742 generations without the occurrence of con-
jugation. It thus appears that a change in the environment
may result in a rejuvenescence of the race.
As a consequence of these experiments, Calkins has sug-
gested that the purpose of conjugation may be to bring about
the union of individuals which have lived in different environ-
ments, and so to produce a renewal of vitality in the same kind
of way as a change in the environment itself.
Calkins differs from Maupas in stating that diverse ancestry
is not essential in order that conjugation may occur, since he
obtained as large a percentage of successful endogamous as
exogamous pairings, and carried one endogamous ex-conjugant
through 379 generations. On the other hand, there is some
evidence that conjugation does not result in rejuvenescence when
both gametes have lived for a long time in the same medium,
so that their chemical composition is too similar.3
1 Simpson (J. Y.), " Observations on Binary Fission in the Life-History
of the Ciliata," Proc. Roy. Soc. Edin., vol. xxiii., 1901.
2 Calkins, "Studies on the Life-History of Protozoa," IV., Jour, of Exp.
Zool., vol. i. , 1C04. (Keferences to earlier papers are here given. See also Biol.
Bull., vol. xi., 1906.)
3 Cull, " Rejuvenescence as a Result of Conjugation,1' Jour, of Exp. Zool.,
vol. iv., 1907. Blackman ("The Nature of Fertilisation," British Assoc.
Reports, York Meeting, 1906) is of opinion that the rejuvenescence theory
of fertilisation is difficult to apply generally in view of the large number of
THE PHYSIOLOGY OF REPRODUCTION
According to Enriques,1 however, conjugation in Colpoda steini
only takes place under certain environmental conditions (e.y. if the
layer of the water is not thicker than two millimetres) and does not
occur at all if the conditions of life are stationary, the infusorians
going on multiplying indefinitely and the number of divisions
from the last conjugation making no difference.2 According to
Woodruff,3 on the other hand, a varied environment seemed to
obviate the necessity for conjugation in Paramcecium.
It may seem a far cry from the Ciliate Infusorian to the
British thoroughbred horse, yet there is evidence that here also
an in-bred and relatively infertile race may be rejuvenated
through access to new surroundings. Allison, referring to
blood stock of British origin, born in Australia and New
Zealand, writes as follows : " We can draw from these, not only
strains of blood which we have lost, but horses and mares,
born again, so to speak, and admirably suited to strengthen and
regenerate our home stock." 4 The same result is said to have
been achieved in the descendants of British horses (especially
hackneys) imported into Argentina.5
The case of the Porto Santo rabbits and that of the goats
of Juan Fernandez, which are cited by Huth 6 as evidence that
in-breeding is harmless, may perhaps be similarly explained.
THE SUPPOSED CHEMOTACTIC PROPERTIES OF SPERMATOZOA AND
THEIR RELATION TO THE PHENOMENA OF FERTILISATION
It has been suggested that the spermatozoon is attracted
towards the ovum by a chemotactic action which the metabolic
products of the latter are able to exert upon the former.
plants in which the fusing cells or nuclei are closely related. The force of
this objection must be admitted. If, however, the conjugating cells have
been subjected to slightly different environmental influences, this near
relationship is not necessarily a difficulty. * Enriques, loc. cit.
2 If water from a culture in which conjugation is " epidemic " be added
to a normal culture, it is stated to induce conjugation. Conversely, if water
from a normal culture is added to a "conjugation culture," it inhibits it.
3 Woodruff, "The Life Cycle of Paramoecium when Subjected in Varied
Environment," Jour, of Exp. Zool., vol. xlii., 1908.
4 Allison, The British Thoroughbred Horse, London, 1901.
5 Wallace (R.), Argentine Shows and Livestock, Edinburgh, 1904. Cf.
also Darwin, Animals and Plants, London, 1905.
• Huth, The Marriage of Near Kin, 2nd Edition, London, 1887.
FERTILISATION
Pfeffer's experiments 1 upon the spermatozoa of ferns are usually
cited as evidence of this view.
Pfeffer observed that malic acid, when put into a capillary
tube with one end open and placed in a drop of liquid con-
taining fern spermatozoa, has a strong attractive influence upon
these organisms, causing them to swim in large numbers into
the opening of the tube. He concluded, therefore, that it is
the malic acid in the archegonium of the fern's ovum which
causes the approach of the spermatozoa.
According to Strasburger,2 the ova of the Fucaceae also
possess chemotactic properties, attracting the spermatozoa from
a distance equal to about two diameters of an ovum. Bordet,3
however, who likewise experimented upon the Fucacese,
obtained no evidence of chemotactic attraction, but he found,
on the other hand, that the sperms were very sensitive to
contact.
Jennings,4 in the course of his experiments on the behaviour
of the Protozoa, has shown that these organisms will tend to
collect in a drop of acid placed in water. This is due to the fact
that, whereas no reaction takes place when the individuals pass
from water to acid, there is a distinct reaction in passing in the
reverse direction. All the organisms which enter the drop of
acid remain there, and consequently they accumulate, but this
is not due to any attractive influence on the part of the drop.
It is of course possible that Pfeffer 's observations on the sup-
posed attraction possessed by malic acid for the spermatozoa of
ferns is susceptible of a similar explanation.
Buller,5 who has discussed the question at some length and
has performed numerous experiments, states that, so far as he is
aware, not a single case is known where chemo taxis plays a part
in the fertilisation of the ova of animals.
1 Pfeffer, " Locomotorische Richtungsbewegungen durch chemische Reize,"
Untersuchungen aus. d. Bot. Inst. zur Tubingen, vol. i., 1884.
2 Strasburger, Das botan. Prakticum, Berlin, 1887.
3 Bordet, " Contribution a 1'Etude de 1'Irritabilite des Spermatozoides
chez les Fuccacees," Bull, de I'Acad. Belgique, vol. xxxvii., 1894.
4 Jennings, " Studies of Reactions to Stimuli in Unicellular Organisms,
Amer. Jour, of Phys., vol. xxi., 1897.
5 Buller, " Is Chemotaxis a Factor in the Fertilisation of the Eggs of
Animals?" Quar. Jour. Micr. Science, vol. xlvi., 1902.
216 THE PHYSIOLOGY OF REPRODUCTION
ARTIFICIAL AIDS TO FERTILISATION
It has been already recorded that cross-fertilisation between
certain species of Echinoderms can be effected by having re-
course to physico-chemical methods. It is not surprising, there-
fore, that fertilisation between individuals belonging to the same
species can be assisted, or caused to take place more frequently,
in the presence of certain substances artificially added.
Thus, according to Roux, frog's eggs can be fertilised more
readily by adding saline solution to the water in which they
are deposited. Wilson says that in the case of the mollusc
Patella, a larger number of eggs can be fertilised if potash
solution is added.1 Dungern 2 states that the activity of
the spermatozoa in the sea-urchin can be increased in the
presence of substances extracted from the ova. Similarly it
is said that normal prostatic secretion has an exciting action
on mammalian spermatozoa (p. 236). Furthermore, Torelle
and Morgan 3 have shown that the immature spermatozoa
of starfish can be stimulated, and fertilisation can be induced,
by adding ether and various salt solutions to the sea- water.
ARTIFICIAL PARTHENOGENESIS
The fact that the ova of various kinds of organisms are
capable under certain circumstances of segmenting and de-
veloping into new individuals without the intervention of male
germ-cells, has been already referred to. In such animals as
the Aphidae this method of reproduction appears to be called
forth by certain conditions of temperature and moisture. In
other forms of life the necessary factors for the occurrence of
parthenogenesis are not so evident, but the fact of its existence
has been known from early times.4
In many animals parthenogenesis has been observed to occur
1 For further information on this subject, with references to literature, see
Przibram, Embryogeny, English Translation, Cambridge, 1908 ; and Jenkinson,
Experimental Embryology, Oxford, 1909.
2 Dungern, " Neue Versuche zur Physiologic der Befruchtung," Zeitschr.
f. allgem. Phys., vol. i., 1902.
3 Morgan, Experimental Zoology, New York, 1907.
4 See footnote, p. 131.
FERTILISATION 217
occasionally, although it may never have become a confirmed
physiological habit. The silkworm moth (Bombyx mori) affords
an example of this phenomenon. In the higher animals also it
has been shown that unfertilised eggs may very abnormally starT
to segment without any obvious source of stimulus. Janosik l
has recorded segmentation in the ovarian ova of Mammals, but
it is doubtful whether such cases should be regarded as truly
parthenogenetic in nature.
Tichomiroff 2 showed that the unfertilised eggs of the silk-
worm moth, which, as just mentioned, is occasionally partheno-
genetic, can be caused to develop in greatly increased numbers
by rubbing them lightly with a brush, or by dipping them for
about two minutes in strong sulphuric acid, and then washing
them. Perez 3 subsequently made some similar observations,
noting also that normal parthenogenetic development was
commonest in those individuals which were most robust.
Richard Hertwig 4 was the first to show that if the ova of
various Echinoderms are treated with certain reagents, and
then restored to normal sea-water, they will frequently display
signs of segmentation. The particular reagent originally
employed by Hertwig was a Ol per cent, solution of sulphate of
strychnine. Not long afterwards Mead 5 observed that the eggs
of the marine Annelid, Chcetopterus, which ordinarily become
mature only after the entrance of the spermatozoa, could be
induced to throw out their polar bodies by adding potassium
chloride to the sea-water in which they were placed.
Morgan 6 found that an addition of sodium chloride to sea-
water containing ova of sea-urchins caused these to form astro-
spheres, while, if the ova were afterwards transferred to ordinary
1 Janosik, "Die Atrophie der Follikel," &c., Arch. f. Mikr. Anat.,
vol. xlviii., 1896.
2 Tichomiroff, " Die kiinstliche Parthenogenese bei Insekten," Arch,
f. Anat. inPhys., Phys. Abth., Suppl., 1886.
3 Perez, " Des Effets des Actions mecaniques sur le Developpement des
(Eufs non-feconde," &c., Proces-Verbaux de la Soc. des Sciences de Bordeaux,
1896-97.
4 Hertwig, " Ueber Befruchtung und Conjugation," Verhandl. der Deutsch.
Zool. Gesellsch., 1892.
5 Mead, Lectures delivered at Wood's Soil, Boston, 1898.
6 Morgan, "The Action of Salt Solutions on the Unfertilised and Fertilised
Ova of Arbacia," &c., Arch.f. Entwick.-Mech., vol. iii., 1896, and vol. viii., 1899.
218 THE PHYSIOLOGY OF REPRODUCTION
sea? water, they sometimes proceeded to segment. The latter
process, however, was not normal, since the ova that had been
subjected to this treatment became transformed into masses of
minute granules, and, instead of acquiring cilia and giving rise to
embryonic individuals, they underwent a process of disintegration.
To Loeb belongs the credit of having done more than any
other worker to elucidate the physico-chemical aspects of the
phenomena of fertilisation. Loeb was the first definitely to
succeed in producing plutei from the unfertilised eggs of the
sea-urchin. His original method was to expose the eggs for
about two hours to sea-water in which the degree of concentra-
tion had been raised by about forty or fifty per cent. This
effect could be produced by the addition of sodium chloride, but
it was found to be immaterial what particular substance was
employed to raise the concentration, so long as it was one which
did not act injuriously on the eggs. The ova were afterwards
restored to normal sea-water, when they began to undergo
segmentation and subsequently developed into normal plutei.
Loeb was able to show, further, that the parthenogenetic
development of the ova in such cases was brought about by a loss
of water. Thus, when the concentration of the sea-water was
less than forty per cent., some of the ova of the sea-urchin Arbacia
could be induced to develop, even though they were allowed to
remain in the hypertonic solution. By adopting similar methods
a like result could be effected for the other species of sea-urchin,
and also in the case of the starfish Asterias jorbesii ; but it was
necessary, as a general rule, to restore the ova to normal sea-
water, as the continuance of abnormal conditions, although it
might not hinder segmentation, usually arrested the further
course of development.1
It was found, however, that osmotic fertilisation differed
in several respects from fertilisation by a spermatozoon.
Firstly, the ova fertilised by the former method began to seg-
1 Loeb (J.), "On the Nature of the Process of Fertilization," &c., Amer.
Jour, of Phys., vol. iii., 1899. "On the Artificial Production of Normal
Larvae from the Unfertilised Eggs of the Sea-Urchin (Arbacia)" Amer. Jour, of
Phys., vol. iii., 1900. " On Artificial Parthenogenesis in Sea-Urchins," Science,
vol. xi., 1900. " Further Experiments on Artificial Parthenogenesis," &c.,
Armr. Jour, of Phys., vol. iv., 1900. These papers are reprinted in Loeb's
Studies in General Physiology, vol. ii., Chicago, 1905.
FERTILISATION 219
ment without developing a membrane such as is invariably
formed in normal eggs shortly after the entrance of the sper-
matozoa. Secondly, the rate of development in the artificially^
fertilised eggs was considerably slower than in the eggs fertilised
by spermatozoa. Thirdly, the larvae arising from osmotic
parthenogenesis, as soon as they began to swim, did so at the
bottom of the dish in which they were placed, instead of rising
to the surface of the water like normal larvae. It was found
also that the percentage of eggs which could be induced to
develop by the osmotic process was invariably very much
smaller than the percentage of normally fertilised eggs which
underwent development. The consideration of these differences
led Loeb to conclude that the spermatozoon in normal fertilisa-
tion carried into the ovum not one, but several substances or
conditions, each of which was responsible for a part only of
the normal characteristics of the process ; and that, in order to
imitate successfully the action of the sperm, it would be necessary
to combine two or more artificial methods.
When the eggs of Strong ylocentrotus purpuratus were put into
50 cubic centimetres of sea- water to which 3 c.c. of a deci-
normal solution of a fatty acid had been added, and were left
in this water for about a minute, and were then transferred to
ordinary sea- water, they were observed to form membranes.
It was also noticed that the eggs underwent internal changes
characteristic of nuclear division, but they were rarely seen to
segment. Subsequently they began to disintegrate, and after
twenty-four hours were nearly all dead. If, however, the ova,
after they had formed a membrane, were deposited in sea-
water which had been rendered hypertonic by adding 15 c.c.
of sodium chloride solution of two and a half times the normal
concentration, to 100 c.c. of sea-water, all or nearly ah1 the eggs
could be induced 'to develop. Furthermore, the rate of de-
velopment was practically the same as that of normally fertilised
eggs, a large percentage of the blastuke looked normal and rose
to the surface of the water, and the plutei which developed
showed the usual degree of vitality.
The brothers Hertwig l had previously discovered that sea-
1 Hertwig (O. and R.), Untersuchungen zur Morphologic und Physiologie
der Zelle, Jena, 1887.
220 THE PHYSIOLOGY OF REPRODUCTION
water saturated with chloroform induced the unfertilised
eggs of the sea-urchin to develop membranes. Herbst l more
recently showed that benzol, toluol, creosote, or oil of cloves
produced a similar effect. Loeb 2 found that amylene and various
other hydrocarbons and acids also called forth membrane forma-
tion, and that eggs which were subjected to these methods
could be made to segment by subsequent treatment with hyper-
tonic sea-water in the way described. The substances which
called forth membrane formation can be divided into two
groups, the first consisting of hydrocarbons and certain sub-
stitute products, and the second being comprised of certain
acids. Loeb states also that the order in which the two agencies
are employed is of vital consequence, for if the eggs are sub-
jected to the membrane-forming solution after being placed in
the hypertonic sea- water instead of before, they develop a
membrane, but shortly afterwards disintegrate. As a result
of this series of experiments he concludes that the process of
membrane formation is an essential and not a secondary pheno-
menon.3 He makes the further suggestion that membrane
formation is brought about by a kind of secretory process, due
to the squeezing out under pressure of a liquid substance from
the interior of the ovum 4 (cf. Jenkinson, p. 189). According to
this view the excretion of the fluid is the essential feature, while
the actual formation of the membrane is probably only a
secondary mechanical effect of the sudden secretion.
In the case of the starfish it was found that the process of
artificial membrane formation was alone sufficient to induce
parthenogenetic development without any further treatment
with hypertonic sea-water. This observation is connected by
Loeb with the fact that starfish eggs are sometimes able to
develop in the absence of any external cause or agency.
1 Herbst, "Uber die kunstliche Hervorragung von Dottermembranen,"
&c., Biol. Centralbl., vol. xiii., 1893.
2 Loeb, The Dynamics of Living Matter, New York, 1906. This work
contains further references. " On an Improved Method of Parthenogenesis,"
Univ. of California Publications : Physiology, vol. ii., Berkeley, 1904.
3 It was found, however, that in the case of the starfish a very small
number of eggs could develop without first forming a membrane, and that
this number could be increased by transitorily treating the eggs with
acidulated sea-water. See below.
4 Loeb,"Ueber die Natur der Losungen," &c.,Pfluger's Arch. , vol. ciii., 1904.
FERTILISATION
Parthenogenetic development of starfish eggs has been produced
also by mechanical agitation ; l but it is possible, as Loeb ob-
serves, that the diffusion of carbonic dioxide, or some other gasj_
into or from the eggs may be the real exciting cause.2
Loeb found also that the unfertilised eggs of the Annelid,
Chcetopterus, could be made to develop into swimming larvae
by adding a small quantity of a soluble potassium salt to the
sea- water in which they were placed.3 The same result could
be brought about by the addition of hydrochloric acid. The
eggs appeared to undergo development, as far as the trochophore
stage, but without segmenting.
Lillie,4 however, found that the nuclear divisions were
abnormal, and that the apparent trochophore larvae were
not typical, being in reality merely " ciliated structures "
which were far behind the real larvae in organisation. But
Bullot 5 showed that in another Annelid, Ophelia, ova fertilised
by hypertonic sea- water underwent a regular segmentation.
Loeb has shown that the ova of limpets (Acmcea and Lottia)
could be artificially fertilised by the combined action of fatty
acid and hypertonic sea-water. This method also had the
effect of hastening maturation, since ova which could not be
fertilised by spermatozoa could be made to develop into larvae
by the artificial treatment. It was found, further, that matura-
tion could be induced by the action of alkaline sea-water, and
that ova which were treated in this way could be fertilised by
spermatozoa or artificially fertilised.6
Bataillon 7 states that the unfertilised eggs of the lamprey,
and also those of the frog, can be made to undergo segmentation
1 Mathews," Artificial Parthenogenesis produced by Mechanical Agitation,"
Amer. Jour. ofPhys., vol. vi., 1901.
2 Loeb, The Dynamics of Living Matter, New York, 1906.
3 Loeb, " Experiments on Artificial Parthenogenesis in Annelids," &c.
Amtr. Jour, of Phys., vol. iv., 1901.
4 Lillie, " Differentiation without Cleavage in the Egg of the Annelid,
Chcetopterus pergamentaceus," Arch. f. Entwick.-Mechanik, vol. xiv., 1902.
5 Bullot, " Artificial Parthenogenesis and Regular Segmentation in an
Annelid (Ophelia) ," Arch. f. Entwick.-Mtchanik, vol. xviii., 1904.
6 Loeb, Univ. of California Publications: Physiology, Berkeley, vol. i.,
1903, and vol. iii., 1905.
7 Bataillon, " Nouveaux Essais de Parthenogenese experimentale chez les
Vertebres inferieurs (Rana fusca et Petromyzon planeri "), Arch. f. Entwick.-
Mechanik, vol. xviii., 1904.
222 THE PHYSIOLOGY OF REPRODUCTION
as far as the morula stage by depositing them in a salt solution
of such a concentration that they lose water. Sugar solutions
were also found to be effective.1
Various experiments have been tried with the object of
finding out whether ova could be fertilised by substances arti-
ficially extracted from spermatozoa, but so far without any
positive result.2 Thus Gies attempted to obtain an enzyme
from spermatozoa, with a view to seeing if such a substance
would exert any influence on the unfertilised ovum, but his
experiments lent no support to the idea.3 Pizon's 4 experiments
on the same question were also negative in result. (See p. 299.)
Loeb 5 has discussed at some length the question as to
whether any idea can be formed regarding the nature of the
action of the spermatozoon in causing the ovum to develop.
He states his belief that " the essential effect of the sperma-
tozoon consists in the transformation of part of the proto-
plasmic or reserve material in the egg into the specific nuclein
or chromatin substance of the nucleus. In each nuclear
division one half of the mass of each original chromosome goes
into the nucleus of each of the two resulting cells. But during
the resting period which elapses until these nuclei are ready to
divide again, each chromosome grows to its original size, and
then a new division occurs. It is quite possible that the oxygen
which is required for the process of cell division is needed for
the synthesis of nuclein or chromatin substance. The fact that
the rate of development is influenced by temperature, in much
the same way as are chemical reactions, supports the idea given
above that the essential feature of fertilisation consists in the
starting or the acceleration of a chemical reaction which is
going on steadily in the egg. Loeb was disposed to conclude,
therefore, that the spermatozoon acts as a positive catalyser,
but further evidence has led him to reject this idea as im-
probable. He points out that, if it were correct, normal sea-
1 Loeb, loc. cit.
2 See Loeb, The Dynamics of Living Matter, New York, 1906.
3 Gies, "Do Spermatozoa contain Enzyme having the Power of causing
Development of Mature Ova? " Amer. Jour, of Phys., vol. vi., 1901.
4 Pizon, " Recherches sur une pratendue Ovulase des Spermatozoides,"
C. R. de I'Acad. des Sciences, vol. cxli., 1905.
5 Loeb { J:), loc. cit.
FERTILISATION
urchin eggs should segment if kept for a sufficiently long period,
and that it ought to be possible to induce segmentation by
applying heat, since heat is known to accelerate chemical re-
actions, but neither of these results could be obtained.
He then suggests the possibility that the spermatozoon, in
'conjugating with the ovum, removes from the latter a negative
catalyser or condition whose existence in the ovum somehow
inhibits the process of development. This suggestion seems to
provide an explanation of the secretory phenomena, which, on
Loeb's hypothesis, are the cause of the membrane formation.
" Finally, we may be able to understand a fact which [has been]
observed in the eggs of a starfish, and which has not yet been
mentioned, when the eggs of Asterina or Asterias are allowed to
ripen, they will die within a few hours unless they develop
either spontaneously or through the influence of sperms or
some of the above-mentioned agencies. The disintegration
which leads to the death of the non-developing egg is obviously
due to an oxidation, since I found that the same eggs when
kept in the absence of oxygen will not disintegrate. We know
that oxygen is an absolute prerequisite for the development
of the fertilised egg " [but this statement is disputed by Delage].
The fact that oxygen is a poison for the mature but non-
developing egg shows that the chemical processes which occur
in the unfertilised, non-developing egg must be altogether
different from those which go on in the developing egg of the
star-fish.1
1 Loeb, loc. cit. See also " The Toxicity of Atmospheric Oxygen for the
Eggs of the Sea-Urchin after the Process of Membrane Formation "; "On
the Necessity of the Presence of Free Oxygen in the Hypertonic Sea-water
for the Production of Artificial Parthenogenesis" ; " On the Counteraction of
the Toxic Effect of Hypertonic Solutions upon the Fertilised and Unfertilised
Egg of the Sea-Urchin by lack of Oxygen," Univ. of California Publications :
Physiology, vol. iii., 1906. See also " Versuche tiber den Chemischen
Charakter des Befruchtungsvorgangs," Biochem. Zeitschr., vol. i., 1906.
" Weitere Beobachtungen Uber den Einfluss der Befruchtung und der Zahl
der Zellkerne auf die Saurebildung im Ei," Biochem. Zzitschr., vol. ii. 1906 ;
"Uber die Superposition von kiinstlichenParthenogenese und Samenbefruch-
tung in derselber Ei," Arc\. f. Entwick.-Mechanik, vol. xxiii., 1907 ; "Uber
die allgemeinen Methoden der kunstlichen Parthenogenese," Pfliljer's Arch.,
vol. cxviii., 1907 ; and other papers in the same volume. The following
papers also deal with artificial parthenogenesis in various animals: Delage,
C. R. de VAcad. des Sciences, vol. cxxxv., 1902 (describing fertilisation by
THE PHYSIOLOGY OF REPRODUCTION
Loeb's general conclusion is that the phenomenon of fertilisa-
tion (as studied in the sea-urchin, the star-fish, Lottia, Polynoe
and Sipunculids) consists essentially, firstly, in a liquefaction
or hydrolysis (or both) of certain fatty compounds in the ovumi
and secondly, in an initiation in the right direction of a new
process of oxidation.1 These changes which occur in the
fertilised egg lead to the synthesis of nuclein material from the
protoplasm. According to this view, the process of astrosphere
formation is not the direct effect of the act of fertilisation, but
is a secondary consequence of the new chemical changes which
are brought about by the entrance of the spermatozoon.2
Delage,3 however, has recently adduced experimental
evidence, some of which is opposed to Loeb's interpretation
of the observed phenomena. This investigator has shown that
ansesthetisation with carbon dioxide during maturation) : and C. R. dc V Acad.
des Sciences, vol. cxli., 1906 (describing fertilisation with various salt solu-
tions) ; Treadwell, " Notes on the Nature of Artificial Parthenogenesis in the
Egg of Patella obscura, Biol. Bull., vol. iii., 1902 ; Scott, " Morphology of the
Parthenogenetic Development of Amphitrite," Jour, of Exper. Zool, vol. iii.,
1906 ; Lefevre, " Artificial Parthenogenesis in Thalassema nifllita," Jour, of
Exper. Zool'., vol. iv., 1907 ; Kostanecki, " Zur Morphologic der kiinstlichen
parthenogenetischen Entwicklung bei Mactra," Arch. f. Mikr. Anat.,
vol. Ixxii., 1908. See also Mathews, whose paper has been already referred
to (Chapter IV. p. 134, "A Contribution to the Chemistry of Cell Division,
Maturation, and Fertilisation," Amer. Jour, of Phys., vol. xviii., 1907). This
author lays stress on the part played by the centriole, and suggests " that the
various methods employed to produce artificial parthenogenesis do not do so
by their direct physical action on the cell, but indirectly by producing in one
way or another active centriole substance in the cell cytoplasm, or by causing
its discharge from the nucleus."
1 Loeb, "The Chemical Character of the Process of Fertilisation and its
bearing upon the Theory of Life Phenomena." — Address before the Interna-
tional Congress of Zoologists, Boston, 1907, Univ. of California Publications,
vol. iii., 1907.
8 Since this was written, Loeb has elaborated his theory further in an
important work recently published, in which full references are given
( Die chemische Entwicklung serregung des tierischen Eies, Berlin, 1909). Membrane
formation is regarded as an essential factor in normal fertilisation, and
is of the nature of a cytolysis of the egg, for all cytolytic agents produce
it. Normally the fertilisation membrane is brought about by a lysin carried
in by the sperm, which also carries another substance that serves to coun-
teract the evil effects of membrane formation. See p. 301, Chapter VIII.,
where the subject is discussed further.
3 Delage, " Les Vrais Facteurs de la Parthe"nogenese Experimentale,"
Arch, de Zool. Exper. et Gen., vol. vii., 1908.
FERTILISATION 225
it is possible artificially to fertilise sea-urchins' eggs by treating
them with solutions of tannin and ammonia. He had already
formed the conception that the essential facts of cell division
could be resolved into a succession of processes involving
coagulation and liquefaction. The formation of the vitelline
membrane is said to be essentially a coagulative process (and
also possibly the formation of the centrosome and of the nuclear
spindle), arid the dissolution of the nuclear membrane and
certain of the accompanying events are regarded as evidence
of liquefaction. These considerations led Delage to employ
tannin as an agent for inducing coagulation, and ammonia for
causing liquefaction. Tannate of ammonia was found to pro-
duce a similar effect, but this is explained by Delage on the
assumption that, since tannin is a feeble acid and ammonia is a
feeble base, the ammonium tannate becomes dissociated, so
that the acid function (which brings about coagulation) and
the alkaline function (which causes liquefaction) may be sup-
posed to co-exist in the solution, and so separately to exert an
influence on different parts of the egg. By adopting the above-
described method, Delage succeeded in artificially fertilising
ova, so that they developed into complete sea-urchins, but it is
curious to note that the symmetry of these individuals was
liable to be abnormal, one of them being hexameral instead of
pentameral. Delage also obtained successful results by using
carbon dioxide and other agents, and star-fishes' eggs as well
as sea-urchins' were successfully fertilised. Furthermore,
certain of the experiments seem to indicate that the presence
of oxygen is not a necessary factor (as supposed by Loeb),
since development could be induced after practically all the
oxygen present had been eliminated.
It is, of course, obvious that Loeb's interpretation of the
observed phenomena of fertilisation among the Metazoa is
inapplicable to the process of game tic union in the Protozoa,
in which the conjugating units are often apparently similar
and equipotential, and the same objection may be offered to
Delage's theory. It is possible, however, that conjugation in
the Protozoa, while presenting an essential similarity to fertilisa-
tion in the Metazoa, initiates a series of chemical processes of a
relatively simpler kind. Moreover, the theory that the changes
THE PHYSIOLOGY OF REPRODUCTION
consequent upon game tic union are the result of a catalytic
chemical reaction is in no way opposed to the vaguer physio-
logical conception that the object of the process is to secure
a rejuvenescence of vital substance without which the race
cannot be perpetuated.
The cytological changes which occur in artificially fertilised
ova have been dealt with at considerable length by Wilson, to
whose paper l the reader is referred. It is shown that the ovum
of the sea-urchin, under an appropriate stimulus, is able to
construct the complete mechanism of mitotic cell division
without the importation of a sperm-centrosome, but beyond
this a multitude of aberrations are exhibited. The number of
chromosomes is one-half that occurring in normally fertilised eggs,
being in the sea-urchin eighteen instead of thirty-six. The cen-
trosomes are primarily formed de novo. According to Delage,2
however, the number of chromosomes in artificially fertilised
sea-urchins becomes eventually restored to the normal by a
process of auto-regulation.
1 Wilson, " Experimental Studies in Cytology : I. A Cytological Study of
Artificial Parthenogenesis in Sea-Urchin Eggs," Arch. f. Entwick.-Mechanik,
vol. xii., 1901. For an account of the cytological phenomena in normal
parthenogenetic eggs, especially in insects, see Hewitt, " Cytological Aspects
of Parthenogenesis in Insects," Memoirs and Proc. Manchester Literary and
Philosophical Soc., vol. 1., 1906.
2 Delage, "Etudes experimentales sur la Maturation Cytoplasmique chez
les Echinodermes," Arch, de Zool. Exper. et. Qgn., vol. ix., 1901. Cf. also
Tennent and Hogue, " Studies on the Development of the Starfish Egg,"
Jour, of Exp. Zool., vol. iii., 1906.
CHAPTER VII
THE ACCESSORY REPRODUCTIVE ORGANS OF THE MALE
AND THE MECHANISMS CONCERNED IN INSEMINATION
" Mais, par ce moyen de propagation seminale, demeure es enfans ce
qu'estoit de perdu es parens et es nepveux ce que de"perissoit es enfans, et
ainsi successivement." — RABELAIS.
A BEIEF description of the mammalian testis has already been
given in a chapter on the physiology of the spermatozoon
(p. 166). It remains, however, to state what is known regarding
the functional relations of the accessory male organs, and to
refer incidentally to the homologous structures in the female.
After traversing the tubules of the rete testis the spermatozoa,
swimming in the seminal fluid, make their way into the vasa
efferentia, which open into the canal of the epididymis. The
vasa efferentia in Man are about twenty in number. Before
passing into the epididymis they become convoluted, forming
the coni vasculosi. Both the vasa efferentia and the tube of
the epididymis contain smooth muscular fibres in their walls.
They are lined internally by columnar epithelial cells provided
with long cilia, which assist the muscles in expelling the semen.
Passing away from the epididymis, and in continuation with
its canal, is the vas deferens, which is nearly two feet long in
the human subject, and has an average diameter of about one-
tenth of an inch. It possesses a plain muscular wall, consisting
of an outer layer of longitudinal, a middle of circular, and an
inner of longitudinal muscles. On the inside of the muscles
there is a mucous coat lined by a columnar epithelium, which is
not ciliated.1
1 Arising from the lower, part of the epididymis, or from the vas deferens
close to its commencement, is a long narrow diverticulum which ends blindly.
This is the vas aberrans. It is probably a vestigial structure. A few small
convoluted tubes, situated near the head of the epididymis and representing
vestiges of part of the Wolffian body, are called the paradidymis or organ of
Giraldes. The innervation of the vas deferens is described below in dealing
with the process of ejaculation.
227
228 THE PHYSIOLOGY OF REPRODUCTION
A branch from one of the vesical arteries accompanies the
vas deferens, and eventually enters the testis, where it anas-
tomoses with the spermatic artery. The vas deferens, near its
termination, becomes sacculated, and in this region is known as
the ampulla of Henle. In the walls of the ampulla there are
•rr
FIG. 53. — Passage of convoluted seminiferous tubules (a) into straight tubules,
and of these into rete testis (c), (after Minalkowicz, from Schafer) ; 6,
fibrous stroma continued from mediastinum.
a number of small tubular glands, which doubtless supply some
portion of the ejected fluid.
Disselhorst 1 believes that the ampulla acts as a seminal
reservoir (a function which has also been assigned to the
vesiculse seminales, as described below), and states that he has
1 Disselhorst, " Ausfiihrapparat und Anhangsdriisen der Miinnlichen
Geschlechtsorgane," Oppel's Lehrbuch der V rgleichenden Mikroscopischen
Anatomic der Wirbeltiere, vol. iv. , Jena, 1904.
MALE ACCESSORY REPRODUCTIVE ORGANS 229
found spermatozoa stored up in little pockets in the walls of
this structure in animals during the rutting time. He suggests,
further, that there is a relation between the state of develop^
ment of the ampulla and the time occupied by copulation.
When the organ is small or absent, as in dogs, cats, and boars,
the coition is a slow process, but when the ampulla is large and
FIG. 54. — Transverse section through the tube of the epididymis.
(After Szymonowicz, from Schafer.)
a, blood-vessel ; 6, circular muscle fibres ; c, epithelium.
well-developed, as in horses and sheep, the coitus occupies a
relatively short time.
The vas deferens on either side unites with the terminating
portion of the corresponding seminal vesicle to form the ejacu-
latory duct. The two ejaculatory ducts, after traversing the
prostate, open into the floor of the urethra by small slit-like
apertures. Their function is to convey to the urethra the
fluid contained in the seminal vesicles and in the vasa deferentia.
230 THE PHYSIOLOGY OF REPRODUCTION
The coats of the ejaculatory ducts are relatively thin. The
lining epithelium is similar to that of the vas deferens.
The urethra, which serves as the common channel for both
urine and seminal fluid, -is lined by a columnar epithelium resting
on a vascular corium. The latter is surrounded by submucous
tissue containing two layers of muscular fibres, the inner
being arranged longitudinally, and the outer circularly. The
FIG. 55. — Transverse section through commencement of vas deferens.
(After Klein, from Schafer.)
a, epithelium ; 6, mucous membrane ; r, d, e, inner, middle, and outer
layers of muscular coat ; /, internal cremaster muscle; <j, blood-vessel.
urethra in man is usually described as consisting of three
divisions, the prostatic, the membranous, and the spongy
portions. Of these the membranous portion comprises that
part of the urethra between the apex of the prostate and the
bulb of the corpus spongiosum, to be described below. Opening
medially into the prostatic portion of the urethra, between the
two ejaculatory ducts, is the aperture of the uterus masculinus,
or organ of Weber, which is the homologue of the vagina and
MALE ACCESSORY REPRODUCTIVE ORGANS 231
uterus in the female. This vesicle, which is a small cul-de-sac,
and in Man lies hidden by the prostate, is probably almost or
quite functionless, but it has a few very small glands which
open into its cavity. In some animals — such as the goat, for
example — it is of comparatively large dimensions, the upper part
being divided into two horns. In connection with it is a
structure corresponding to the hymen of the female. On the
floor of the prostatic portion of the urethra is an elevation of
the mucous membrane and underlying tissue, known as the
crista urethra or caput gallinaginis. This eminence (which con-
tains erectile tissue) serves when distended with blood to
prevent the semen from passing backwards to the bladder,
and mingling with the urine in the process of emission. It is
assisted in this function by the contraction of the sphincter of
the bladder.
The urethra in the female corresponds to that part of the
male urethra which is anterior to the openings of the ejaculatory
ducts. It is lined with a stratified scaly epithelium, like that of
the vagina into which it opens. Communicating with the
female urethra are two complex tubular glands known as
the glands of Skene. Their ducts open very close to the
urethral aperture.
THE VESICUL^E SEMINALES
The seminal vesicles are offshoots from the lower ends of
the vasa deferentia. They consist in Man of coiled tubes, about
five inches long, into which several diverticula sometimes open.
The structure of the vesicles is similar to that of the sacculated
part of the vas deferens, but the muscular layers are relatively
thinner.
There has been some dispute as to the chief function of
the seminal vesicles. According to one view, they serve mainly
as receptacles for the spermatozoa before ejaculation. Most
authorities, however, are disposed to lay greatest stress upon
their secretory function.
Rehfisch * has shown that if fluids are injected into the
1 Kehfisch, "Neuere Untersuchungen tiber die Physiologie der Samen-
blasen," Deutsche med. Wochenschr., vol. xxii., 1896.
THE PHYSIOLOGY OF REPRODUCTION
testicular end of the vas deferens, they first enter the seminal
vesicle and afterwards pass out through the urethra. He
concludes that the vesjculae serve the double purpose of secretory
glands and reservoirs for the semen. Misuraca l states that
in dogs and cats, which have no seminal vesicles,2 the sper-
matozoa disappear from the male passages from five to seven days
after castration, whereas in guinea-pigs, in which the vesicles
are well developed, sperms may be found alive as long as twenty
days after the removal of the testes. This is regarded as
evidence that the seminal vesicles function as receptacles for
the spermatozoa. Moreover, Meckel 3 stated that he found
sperms in the vesiculae of the mole in the month of February
(i.e. during the breeding season) ; and Seubert 4 recorded a
similar observation about the hedgehog in August (also in the
breeding season) (cf. p. 60). Disselhorst,5 however, throws
some doubt on these observations. That the vesiculse may
undergo periodic enlargement in animals which have a rutting
season is, however, an unquestionable fact.
As evidence that the vesiculse seminales are undoubtedly
secretory glands, Lode 6 showed that in young animals, in which
one of the testes had been removed, the corresponding vesicula
continued to grow, and became filled with its characteristic
fluid. It was evident, therefore, that the fluid must have been
secreted in the vesicula in question, since it could not have
been derived from the testis of the other side. (The effects
of complete castration on the growth and activity of the vesi-
culse seminales are briefly referred to below.) Stilling 7 and
1 Misuraca, " Sopra un importante questione relativa alia castrazione,"
Rivista sperimentale di Freniatria, vol. xv., 1890.
2 Seminal vesicles are absent not only in dogs and cats, but in many other
Carnivora, and also in Cetacea and Ruminantia. They are also wanting in
rabbits, but are present in the vast majority of Rodentia (Owen, Comparative
Anatomy, vol. iii., London, 1868).
3 Meckel, Beitrdge zur Vergleichende Anatomic : I. Ueber die Mannlichen
Greschlechtsteile des Maulwurfs. 1809.
4 Seubert, " Symbolum ad Erinacei europsei anatomen," Inaug. Dissert.,
Bonn, 1841.
5 Disselhorst, loc. cit.
6 Lode, " Experimentelle Beitriige zur Physiologic der Samenblasen,"
Sitzungsber. d. kais. Acad. d. Wissenschaft in Wien, vol. civ., 1895.
7 Stilling, " Beobachtungen iiber die Functionen der Prostata und iiber die
Entstehungen prostatischer Concremente," Virchow's Archiv, vol.xcviii., 1884.
MALE ACCESSORY REPRODUCTIVE ORGANS 233
Akutsu l state that the epithelial cells of the vesiculae seminales
change their character according to whether they are in a state
of rest or activity. In the former condition they are larger
and contain more plasma substance. Kolster 2 has described
desquamation of epithelial cells in the seminal vesicles of the
elk (Cervus alces).
The secretion is formed apparently in considerable quantity.
Its character and composition vary somewhat in different
Mammals. In Man it is gelatinous, and consists chiefly of
globulins.3 It has been investigated in Rodents by Sobotta,4
Rauther,5 and others, who describe it as a white or yellowish-
white gelatinous fluid, which becomes almost solid after ejacu-
lation. This capacity to clot is supposed by Landwehr 6 to be
due to the presence of fibrinogen, 27 per cent, of which was
found to be present. Calcium, however, could not be dis-
covered. Camus and Gley 7 state the clotting is brought about
by a specific ferment (which they call vesiculase) in the prostatic
secretion. (See p. 237.)
The clotting of the fluid, after its entrance into the female
passages in Rodents, prevents the escape of the spermatozoa
and so helps to ensure fertilisation. This fact was first dis-
covered by Lataste,8 who speaks of the " bouchon vaginal "
formed by the solidified secretion of the vesiculse. Similar ob-
servations have been made by Leuckart 9 and others. The
1 Akutsu, " Mikroscopische Untersuchung der Secretionsvorgange in den
Samenblasen," Pfluger's Archiv, vol. xcvi., 1903. Further references are
given in this paper.
2 Kolster, " Ueber einen eigenartigen Prozess in den Samenblasen von
Cervus alces," Arch. f. Mikr. Anat., vol. lx., 1902.
3 Furbringer, "Die Storungen des Geschlechtsfunktion des Menschen,"
Nothnagel's Pathologic und Therapie, vol. xix., 1895.
4 Sobotta, " Die Befruchtung und Furchung des Eies der Maus," Arch. f.
Mikr. Anat., vol. xlv., 1895.
5 Kauther, " Ueber den Genitalapparat einiger Nager und Insektivoren,"
&c., Jenaische Zeitsch. f. Naturtvissenschaft, vol. xxxvii., 1903.
6 Landwehr, " Ueber den Eiweisskorper (fibrinogene substanz) der Vesicula
seminalis der Meerschweinchen," Pfluger's Archiv, vol. xxiii., 1880.
7 Camus and Gley, " Note sur quelques faits relatifs a 1'enzyme prostatique
(vesiculase) et sur la fonction des glandes vesiculaires," C. R. de Soc. de BioL,
vol. iv. (10th series), 1897.
8 Lataste, " Sur le bouchon vaginal des Rongeurs," Zool. Anz., vol. vi., 1883.
9 Leuckart, Zur Morphologic und Anatomic der Geschlechtsorgane , Gottin-
gen, 1847.
234 THE PHYSIOLOGY OF REPRODUCTION
" bouchon vaginal " is said to remain in situ for several hours,
and then to become softened and fall out.
Tarchanoff l has suggested that in the frog the filling of the
seminal vesicles serves to excite sexual feeling in the male
during the breeding season, but certain other observations
have been made which seem to disprove this (or at any rate
to show that it is not universally true). Thus, in some
animals, it is known that sexual desire exists before the
seminal vesicles become full. Moreover, Steinach 2 found
that rats, whose seminal vesicles had been removed, still
retained their desire for copulation although their fertility
was diminished.
That the spermatozoa possess complete functional activity
before they can be in any way influenced by the secretion of
seminal vesicles has been conclusively shown by Iwanoff,3 who
induced pregnancy artificially in rabbits, guinea-pigs, and other
animals, by injecting into the female passages fluid obtained
directly from the epididymis, and mixed with a 5 per cent,
solution of sodium carbonate. The diminished fertility in
Steinach's rats, after the removal of the vesiculse, was probably
due to the absence of formation of the " bouchon vaginal/' as
has been suggested by Rauther.4
It would seem probable that, in the majority of animals
which possess vesiculae seminales, the secretion of these glands
serves to dilute the semen, and so assists in providing a fluid
medium for the transference of the spermatozoa.
Exner 5 has suggested that the seminal vesicles may have
the function of absorbing the seminal fluid which is not ejaculated,
but there is little evidence that this is the case.
Lode 6 found that in castrated bulls, horses, and guinea-pigs,
the glandular epithelium of the vesicles atrophied, but the con-
1 Tarchanoff, " Zur Physiologic des Geschlechtsapparates des Frosches,"
Pfliiger's Archiv, vol. xl., 1887.
a Steinach, " Untersuchungen zur Vergleichenden Physiologie der Mann-
lichen Geschlechtsorgane," &c., Pflilger's Archiv, vol. Ivi., 1894.
3 Iwanoff , " La Fonction des Vesicles seminales et la Glande prostatique,"
Jour, de Phys. et de Path. Gen., vol. ii., 1900.
4 Rauther, loc. cit.
5 Exner, " Physiologie der Mannlichen Geschlechtsfunktionen," Frisch and
Zuckenhandl, Handbuch der Urologie, 1903.
6 Lode, loc. cit.
MALE ACCESSORY REPRODUCTIVE ORGANS
nective tissue underwent hyperplasia. Gruber l and Pelikann 2
observed that in castrated men the glands atrophied, but
became filled with a kind of mucous liquid.
THE PROSTATE GLAND
The prostate in Man and other Mammals is a tubular gland
which surrounds the urethra at the base of the bladder, and
opens into it by a number of small ducts situated close to the
FIG. 56. — Section through part of human prostate. (After Heitzmann,
from Schafer,)
C, concretions, often found in old subjects ; E, epithelium ;
M , muscular tissue.
apertures of the ejaculatory ducts. It is usually described as
consisting of three lobes, two lateral and one median, the former
comprising the chief mass of the organ. Associated with the
glandular substance is a considerable quantity of plain muscular
tissue. The prostate is provided with lymph- vessels and blood-
vessels. The arteries arise from the vesical, haemorrhoidal, and
1 Gruber, " Untersuchung einiger Organe eines Castraten," Mailer's
Archiv, 1847.
2 Pelikann, Gerichtl.-mediz. Unters. iiber d. Skopz-ntwn in Russland,
Giessen, 1876.
236 THE PHYSIOLOGY OF REPRODUCTION
pudic arteries. The veins communicate with the dorsal vein
of the penis and with the internal iliac vein. The inner vation
of the gland is described below in dealing with the mechanism
of ejaculation (p. 258).
The prostatic secretion is a viscid, slightly acid liquid
(sometimes neutral or even alkaline), containing proteins
and salts.1 (See p. 287.) The characteristic smell of the
ejected seminal fluid is said to be partly due to the prostate
secretion, which also contributes to the formation of Bottcher's
crystals described below (p. 285).
De Bonis 2 describes the epithelial cells of the dog's prostate
as containing a small number of granules. When these have
been formed in sufficient quantity, so as almost to fill the cell,
its wall ruptures and the granules pass out into the lumen of
the gland. This occurs especially during coitus. After the dis-
charge of the granules fresh ones are formed in the cells of the
gland.
Little is definitely known regarding the function of the
prostate beyond the fact that it contributes additional fluid to
the semen. It may, perhaps, assist in providing the spermatozoa
with nutriment.3 There is some evidence, however, that it
exercises a stimulating influence upon the movements of the
spermatozoa.4 Steinach observed that prostatic fluid, when
added to normal saline solution, kept the spermatozoa in active
movement for a longer period than saline solution alone.
Steinach also found that rats in which the prostate gland,
together with the seminal vesicles, was extirpated, were ab-
solutely sterile,5 but this may have been due to failure to form
a " bouchon vaginal " in the female. As already mentioned
1 Poehl, Die Physiol.-chem. Grundlage der Spermintheorie, St. Petersburg,
1898 ; Fiirbringer, Die Storungen der Geschlechtsfunktion des Mannes,
Wien, 1895 ; Berliner klin. Wochenschrift, vol. xxiii., 1886.
2 De Bonis, " Uber die Sekretionserscheinungen in den Driisenzellen der
Prostata," Arch. f. Anat. u. Phys., Anat. Abth., 1907.
3 It has been suggested also that the prostate is a sphincter of the
bladder, but this is rendered unlikely by its absence in the female. It is more
probable that it serves to cleanse the urethra of urine before copulation.
4 Fiirbringer, loc. cit. Kolliker, " Physiologische Studien liber die Samen-
flussigkeit," Zeitschr. f. wiss. Zool., vol. vii., 1856.
5 Extirpation of the vesiculae seminales alone produced only partial
sterility (see p. 234).
MALE ACCESSORY REPRODUCTIVE ORGANS 237
(p. 233), the clotting which causes the formation of the " bouchon ' '
in Rodents is believed by Camus and Gley l to be due to a fer-
ment (" vesiculase ") which is present in the prostatic fluid_._
The removal of the prostate in Steinach's experiments had
no effect in diminishing sexual desire.
Walker 2 has also adduced experimental evidence pointing
FIG. 57. — Section through prostate gland of monkey.
a, tubular alveolus lined with epithelium ; 6, alveolus containing concretion
in lumen ; c, bundle of muscular fibres in connective tissue ; rf, blood-
vessels in stroma.
to the conclusion that the prostatic fluid of the dog stimulates
the sperms to more active movement.
Iwanoff's experiments 3 (see p. 234), however, show that
spermatozoa which have never come into contact with prostatic
1 Camus and Gley, loc. cit.
- Walker (G. ), " Beitrag zur Kenntniss der Anatomie und Physiologic der
Prostata beim Hunde," Arch. f. Anat. u. Phys., Anat. Abth., 1899.
3 Iwanoff, loc. cit.
238 THE PHYSIOLOGY OF REPRODUCTION
secretion possess full functional activity, and are capable of
fertilising ova successfully.
Serralach and Pares l have adduced evidence indicating that
the prostate is an internally secreting gland which controls the
testicular functions, and regulates the process of ejaculation.
It is stated that if the prostate is removed spermatozoa are no
longer produced in the testis, and that the secretory activity
of the accessory genital glands ceases. These changes, however,
can be prevented by the administration of glycerine extracts
of prostate gland. The experiments were upon dogs. The
most obvious criticism of Serralach and Pares' view is that it is
unlikely, on phylogenetic grounds, that the functional activity
of the essential organ of reproduction should depend on the
presence of an accessory gland of comparatively recent evolu-
tionary development. On the other hand, it is arguable that the
prostate may originally have formed part of the testis, and sub-
sequently have become differentiated as a separate organ in the
course of phylogeny. Reference may be made in this con-
nection to the somewhat similar theory, which certain gynaeco-
logists have held, that the ovarian functions are dependent on
an internal secretion arising in the uterus, whereas the most
recent experimental evidence proves clearly that this is not the
case (see p. 345).
Griffiths 2 has shown that the prostate glands in the hedgehog
and the mole undergo definite cyclical changes which are cor-
related with changes in the functional activity of the testes
(c/. p. 232). In the quiescent state the prostate is composed of
a few tubules lined by small, flattened, epithelial cells, which
are at this time incapable of producing a secretion. With the
approach of the breeding season the tubules grow much larger
and the epithelial cells become columnar. During rut the
prostate gland is a mass of tortuous tubules, and has grown to
many times the size of the quiescent organ. The tubules are
described as being filled with coagulated mucus, containing a
number of small round cells resembling leucocytes ; while the
epithelial cells are said to show numerous mucigenous granules,
1 Serralach and Pares, " Quelques donnees sur la Physiologic de la Prostate
et du Testicule," C. R. de la Soc. BioL, vol. Ixiii., 1908.
2 Griffiths, " Observations on the Function of the Prostate Gland in Man
and the Lower Animals," Jour, of Anat. and Phys., vol. xxiv., 1890.
MALE ACCESSORY REPRODUCTIVE ORGANS 239
especially in the inner or lumen half, but also, though less
markedly, in the outer half of each cell (cf. de BomV description
of the dog's prostate referred to above).1
The prostatic secretion is expelled into the urethra during
the sexual act by the contraction of the sheath of non-striped
muscle which surrounds each tubule throughout its entire length.
It has been shown in both Man and animals that the growth
of the prostate is dependent upon the growth of the testes, since
it remains of small size until the time of puberty, when the
generative system reaches its full development. In those ab-
normal cases in which testicular growth is arrested, the prostate
remains in a condition of rudimentary development. Moreover,
it has been shown that the prostate in Man normally undergoes
atrophy in old age (see p. 676), or as a result of castration,
becoming transformed after a few years into a mass of fibrous
connective tissue containing a small number of scattered muscle
fibres in a state of degeneration. It has been found also that the
prostatic tubules disappear almost entirely in castrated animals,
and what is left of the epithelium completely loses its secretory
function 2 (cf. p. 303). De Bonis' experiments, however, seem to
show that the administration of prostatic extract to castrated
dogs may lead to a renewal of activity and to the formation of
fresh granules in the secretory cells, but this result could not be
obtained by employing testicular extract.
COWPER'S GLANDS
Cowper's glands are situated near the anterior end of the
urethra. They are a pair of small tubulo-racemose glands, and
communicate with the urethra by two ducts, apertures of which
1 See also Griffiths, " Observations on the Anatomy of the Prostate,"
Jour, of Anat. and Phys., vol. xxiii., 1889. For the comparative anatomy
of the prostate, see Oudemans' Die Accessorischen Geschlechtsdrusen der
Saugethiere, Haarlem, 1892. According to this authority, the hedgehog has
two pairs of prostates. The homologies of these glands in Insectivores
still seem to be obscure. See below, under Cowper's glands.
2 Griffiths, loc. cit. Cf. also Griffiths, " The Condition of the Testes and
Prostate Gland in Eunuchoid Persons," Jour, of Anat. andPhys., vol. xxviii.,
1893 ; Walker (G.)," Experimental Injection of Testicular Fluid to prevent the
Atrophy of the Prostate Gland after the Removal of the Testes," Johns Hopkins
Hospital Bull., vol. xi., 1900; Wallace (Cuthbert), "Prostatic Enlarge-
ment," London, 1907 ; de Bonis, loc. cit.
240 THE PHYSIOLOGY OF REPRODUCTION
(in the human subject) are about two inches below the openings
of the vasa deferentia. The lobules of the glands are surrounded
by a firm investing membrane which contains muscular tissue.
They are lined internally by a secretory epithelium.
The significance of the viscous secretion which these glands
produce is still unknown. It has been suggested that it serves
to cleanse the urethra of urine or semen. Since it is poured out
in considerable quantity during coitus, and appears sometimes
to precede the ejaculation of the actual semen, it is not im-
possible that the secretion of these glands may possess the
special function of ridding the urethra of all traces of urine
preparatory to the passage of the spermatozoa. The glands of
Littre or Morgagni, which beset the whole lining membrane of the
urethra, except near the external orifice, probably serve the same
purpose as Cowper's glands. (C/. prostate, footnote 3, p. 236.)
According to Nagel,1 Cowper's glands are of the normal
dimensions in castrated men, and consequently should not be
regarded as purely sexual organs. On the other hand,
Schneidemiihl,2 whom Nagel quotes, says that in animals
they atrophy after castration. Griffiths 3 describes these
glands in the hedgehog and the mole as undergoing periodic
changes similar to those of the prostate glands. In the hedge-
hog the secretion is abundant during the summer (i.e. in the
breeding season), and possesses a disagreeable and penetrating
odour. According to Gley,4 the secretion in this animal contains
a ferment which causes the fluid of the vesicula? seminales to
clot, so that Cowper's glands in the hedgehog are the physio-
logical equivalent of the prostate gland in the Rodentia.5
1 Nagel, " Physiologie der Mannlichen Geschlechtsorgane," NageVs Hand-
buck der Physiologie des Menschen," vol. ii., Braunschweig, 1906.
2 Schneidemuhl, " Vergleichende Anatomische Untersuchungen iiber
denfeineren Bail der Cowperschen Druse," Deutsche Zeitschr. f. Tiermedizin,
vol. vi., 1883.
3 Griffiths, " Observations on the Function of the Prostate Gland," &c.,
Jour, of Anat. and Phys., vol. xxiv., 1890.
4 Gley, "Role les Glandes genitales accessoires dans la Reproduction,"
Nel primo Centenario dalla Morte di Lazzaro Spallanzani Acad. Sci. e
Stranieri, 1899.
5 It should be mentioned that very considerable doubt has been thrown
on the homology of what are often called Cowper's glands (those presumably
referred to by Gley and Griffiths) in the hedgehog with the glands known
by that name in other Mammals. According to Leydig (" Zur Anatomic der
MALE ACCESSORY REPRODUCTIVE ORGANS
Furthermore, Stilling l states that the epithelium of Cowper's
glands undergoes definite histological changes which depend
upon the occurrence of coitus.2
Corresponding to Cowper's glands in the male there are in
the female a pair of small glands situated one on each side of
the vagina. These are the glands of Bartholini or Duverney.
Their ducts open out on to the vulva, on the sides of the
vaginal orifice. These glands secrete a viscid fluid which helps
to moisten and lubricate the surface of the vulva.
In addition to the accessory male glands described above,
there are, in many animals, other glands (perineal, inguinal, and
preputial) which are probably sexual, inasmuch as they are
believed to serve as means of attraction between the sexes
during the breeding season.3 Most of these glands emit secre-
tions of a musky odour, which in the vast majority of cases is
peculiar to the male, and very often to the male during the
rutting season only. Amongst the animals in which this pecu-
liarity occurs are the musk deer and other kinds of deer and
antelopes, the musk rat, the hamster, and many other Rodentia
Miinnlichen Geschlechtsorgane und Analdriisen der Siiugethiere," Zeitschr. f.
iviss. ZooL, vol. ii., 1850), Cowper's glands in the hedgehog are in reality repre-
sented by a pair of glands embedded in the urethral muscle (cf. Oudemans,
loc. cif.). The so called Cowper's glands, which, as mentioned above,
undergo marked cyclical changes, are situated outside the pelvis close
to the ischial tuberosity and the base of the penis (Linton, "A Contribution
to the Histology of the so-called Cowper's Glands of the Hedgehog," Anat.
Anz., vol. xxxi., 1907). In the absence of embryological evidence, Linton
appears to regard these glands as sui generis. They are shown by this
author to be composed of two distinct kinds of secreting acini, one lined
by a single layer of columnar epithelial cell's, and the other by many layers
of polyhedral cells. Both kinds secrete a considerable quantity of fluid,
containing circular bodies which are believed to be the nuclei of disin-
tegrated cells, though no cells in process of disintegration could be found
in the single-layered type of acinus.
1 Stilling, " Uber die Cowperschen Drtisen," Virchow's Arch., vol. c., 1885.
2 For an exhaustive account of the minute anatomy of the accessory
glands and ducts of the male reproductive system in the different groups of
Vertebrata, with full references to the literature, see Disselhorst in QppeVs
Lehrbuch, loc. cit.
3 Tiedemann, Comparative Physiology, English Translation, London,
1834 ; Grosz, " Beitrage zur Anatomic der Geschlechtsdriisen der Insektivoren
und Nager," Arch. f. Mikr. Anat., vol. Ixvi., 1905. See also description of
prepuce (p. 242).
Q
THE PHYSIOLOGY OF REPRODUCTION
and Insectivora. The temporal gland of the elephant is also
stated to emit a sexual secretion, especially in the male during
rut.
THE COPULATORY ORGAN
The penis is the intromittent organ of copulation. Besides
serving to conduct the urine to the exterior through the
channel of the urethra, it has the further function of conveying
the semen into the genital passages of the female. This latter
function is dependent upon its power of erection under the
influence of sexual excitement.
The erectile tissue of the penis is contained chiefly in three
tracts, the two corpora cavernosa, which are situated one on each
side and are united in the middle line, and the smaller corpus
spongiosum, which is placed inferior ly and surrounds the urethral
passage. The corpora cavernosa are enclosed by an invest-
ment, containing plain muscle fibres, numerous well-developed
elastic fibres, as well as bundles of white fibres. Trabecula?
pass inwards from the fibrous sheath and cross the cavities
of the cavernous bodies, dividing them into interstices which are
filled with venous blood, being, in fact, greatly enlarged vessels.
The corpus spongiosum is similar in structure, but its fibrous
framework is not so well developed. The canal of the urethra
is surrounded by plain muscle fibres. Muscular tissue is also
present in the external" coat of the spongy body, and in the
trabeculse.
At their proximal ends the three corpora are enlarged into
bulbs. Those of the cavernous bodies are covered by the
ischio-cavernosi muscles (or erectores penis), while the bulb
of the spongy body is surrounded by the bulbo-cavernosus
muscle (or ejaculator urinse). At its distal end the corpus
spongiosum becomes enlarged, forming the glans penis, which
is identical in structure with the rest of the body.
The integument of the penis in the region of the glans be-
comes doubled in a loose fold. This is the prepuce or foreskin.
Numerous sebaceous glands are present near the free margin
of the prepuce. These glands emit an odoriferous secretion which
in some animals is especially marked during the season of rut.1
1 Courant, " Uber die Praputialdrusen des Kaninchens und tiber Verander-
ungen derselben in der Brunstzeit," Arch. f. Mikr. Anat., vol. Ixii., 1903.
MALE ACCESSORY REPRODUCTIVE ORGANS 243
The penis is very sensitive to external stimulation, its
surface being beset with simple and compound end-bulbs
and Pacinian corpuscles, especially in the region of the glans.
Its innervation is described below.
The arteries of the penis are the internal pudic arteries
and the dorsal artery. Some of the arterial branches project
into the intertrabecular spaces of the corpora cavernosa, and
T.A. /-T-r*?-;
U. A.
FIG. 58.— Transverse section through adult human penis, x 3. (After
Eberth, from Nagel.)
A., artery; C., cutis ; Com., communication between the two corpora
cavernosa ; Corp. Spong., corpus spongiosum ; F., fascia ; N., nerves ;
&., septum ; T. A., tunica albuginea ; Te. Subc., tela subcutanea penis;
Te. Sub/., tela subfascialis ; Tun., tunica dartos penis; Tr., trabeculae
of corpus cavernosum ; U., urethra; F., veins.
form coiled dilated vessels which are known as the helicine
arteries. In most cases the arteries are said to open into the
venous spaces, through the intervention of capillaries, but a
few of the smaller arteries are stated to communicate directly
with the cavernous veins. The blood is carried away by two
sets of veins, the one set uniting to form the dorsal vein, and
the other communicating with the prostatic plexus and the
pudendal veins.
244 THE PHYSIOLOGY OF REPRODUCTION
When the venous spaces in the erectile tissue are distended
with blood the organ erects, becoming hard and rigid in con-
dition. It is this power of erection which enables the penis
to function as an intromittent organ during copulation.
The above description applies more especially to the
copulatory organ in Man. In the other groups of Mammals
it has essentially the same structure, but presents sundry
modifications in the different orders.1 In the Monotremata,
FIG. 59. — Section through erectile tissue. (After Cadiat, from Schafer.)
a, trabeculae ; b, venous spaces ; c, muscular fibres cut across.
however, there is no corpus spongiosum.2 In some Mammals
(Carnivora and Rodentia) the penis is provided with a
1 For an account of the structure of the copulatory organ in the various
groups of Vertebrates, with notes on the different modes of copulation and
bibliography, see Gerhardt, " Morphologische und biologische Studien iiber
die Kopulationsorgane der Saugethiere," Jenaische Zeitschr. f. Natunvissen-
schaft, vol. xxxix., 1905.
2 The penis of the Monotreme is perforated by a canal, through which the
semen passes but not the urine. When in a relaxed state the organ lies in a
little pouch in the floor of the cloaca, from which it projects when erected .
The cloaca is the single common chamber through which the fjeces and
urine pass to the exterior, as in birds and reptiles. In birds the penis is
either altogether absent or else is rudimentary (Crax, Crypturus, Lam el -
lirostres, Katitae), Disselhorst, u Gewichts- und Volumszunahmedermannlichen
Keimdriisen," &c., Zool. Anz., vol. xxxii., 1908.
MALE ACCESSORY REPRODUCTIVE ORGANS 245
:pyji: k
^~d
^^^^^ •
-^^r^^
60. — Part of transverse section through penis of monkey.
erectile tissue ; 6, urethra ; c, artery ; d, nerve ; e, Pacinian body ;
/, fold of epithelium ; g, surface epithelium.
246 THE PHYSIOLOGY OF REPRODUCTION
cartilaginous or bony support, the os penis, which is developed
especially in the region of the glans. It is particularly large in
the walrus. In the Cetacea the penis is often of enormous size
(six feet in length in some species), and terminates in a point,
but is otherwise normal. It can be withdrawn into the body
when not being used. In copulation, whales apply their ventral
surfaces to one another.
In most Rodents and Marsupials the penis in the relaxed
state is withdrawn within an eversible fold of skin which con-
stitutes a dermal sac. When the penis is erected this sac is
everted, and forms its outer integument. Cole has described
the structure of the intromittent sac in the male guinea-pig,
which appears to be typical of many other Rodents.1 Dorsal
to the urethral aperture when the penis is withdrawn, and
ventral to it when it is everted, is seen the entrance to the
intromittent sac. Lying in the cavity of the sac are two
horny styles. Two dorsal longitudinal folds are also noticeable.
These are the backward prolongations of the lateral lips of the
urethral aperture, the ventral lip consisting of corpus spongiosum
and separating the aperture of the urethra from that of the sac.
Attached to the base of the sac are two retractor organs which
consist of elastic fibres and erectile tissue, and are connected
at their other extremities with the integument of the penis.
The eversion of the sac is brought about by the erection of the
two longitudinal folds referred to above. The whole of the
sac is composed largely of erectile tissue, but the tissue of the
longitudinal folds is even more highly erectile than the rest of
the sac. The entire structure is provided with a very rich
nerve supply. When the penis is erect, and the sac everted, the
two horny styles are protruded externally to a considerable
length. Moreover, both the sac and the surface of the glans
are covered with sharp spine-like structures, while in some
species of Caviidre they are provided also with two sharp horny
saws which are appended to the sides of the penis farther back.
There can be little doubt that the purpose of this unique con-
trivance is to act as an exciting organ on the sexual structures
of the female.
1 Cole, " On the Structure and Morphology of the Intromittent Sac of the
Male Guinea-pig," Jour, of Anat. and Phys., vol. xxxii., 1898.
MALE ACCESSORY REPRODUCTIVE ORGANS 247
In another rodent, the marmot, according to Gilbert 1 the
skin which covers the os penis becomes torn away during the
rutting season, so that the bone projects freely beyond the end
of the glans and is then used as a stimulating organ.
Structures which project from the penis, and are probably
employed as sexual irritants, are also found in the rhinoceros,
the tapir, and certain other animals.
In the cat the glans is beset with callous retro verted papillae,
which no doubt serve the same function. They are present also
in the lion and tiger, but are of smaller size.2
Perhaps the most curious modifications presented by the
mammalian organ of copulation are those found in certain
species of Ruminants. In the sheep, the gazelle, the giraffe,
and a number of antelopes, there is a long filiform process
FIG. 61. — Distal end of ram's penis, as seen from the left side, showing
glans and filiform appendage. The prepuce is folded back. Slightly
reduced.
attached to the end of the organ and traversed by the urethral
passage. In some forms the process arises medially (the penis
being symmetrical) ; but in others, such as the sheep, it is
attached to the left side of the organ, the distal end of which
appears to have undergone some sort of torsion.3 The urethra
opens to the exterior at the extreme end of the filiform ap-
pendage. This structure — which has been investigated, especially
in the case of the sheep 4 — is composed largely of erectile tissue
which surrounds the urethra, and may be regarded as an ex-
tension of the corpus spongiosum. Outside the erectile tissue is
a well-marked muscular layer which lies next to the integument.
The process is supported by a pair of fibro-cartilage bodies,
1 Gilbert, " Das Os priapi der Saugethiere," Morph. Jahrbuch, vol. xviii.
2 Owen, On the Anatomy of Vertebrates, vol. hi., London, 1868.
3 Garrod, "Notes on the Osteology and Visceral Anatomy of Ruminants,"
Proc. Zool. Soc., vol. xlv., 1877.
4 Nicolas, "Sur 1'Appareil Copulateur du Belier," Jour, de VAnat. et la
Phys., vol. xxiii., 1887. Marshall, "The Copulatory Organ in the Sheep,"
Anat. Anz., vol. xx., 1901.
THE PHYSIOLOGY OF REPRODUCTION
placed one on each side of the urethra and extending throughout
the whole length of the structure.
The fact that the filiform prolongation is an erectile organ
points to the conclusion that its function is insertion into the os
uteri during copulation. An examination of the uterus in the
sheep shows that the os, when open, is fully large enough to
admit of the entrance of the distal portion of the penis in the
region of the glans. If the extreme distal end does so enter,
the filiform process must extend into the cavity as far, or
BI. v.
Muse.
Int.
Fibr Cart
Ur.
FIG. 62.— Transverse section through filiform appendage of ram, about
a quarter its length from the tip. x 45.
Bl. V,, blood-vessels; Ep. Ur., epithelium surrounding urethral cavity;
Fibr. Cart., fibro-cartilage ; Int.. integument; Muse., muscular layer;
Ur., urethra.
nearly as far, as the junction of the relatively short corpus uteri
with the two cornua. That the appendage functions in the
manner described seems additionally probable in view of the
fact, to which sheep-breeders attest, that if the process is cut
off the ram is rendered barren. Professor Robert Wallace
informs me that it used to be a regular practice, for the pro-
tection of ewes while being driven south from the Highlands of
Scotland, to cut off the filiform appendage from the rams to
prevent them from impregnating the ewes on the way, this
method of inducing sterility proving quite as effective as removal
of the testicles.
MALE ACCESSORY REPRODUCTIVE ORGANS 249
In the bull, the musk ox, and some other Ruminants the
filiform process is vestigial.
Fibr. Cart.
Fibr. Cart.
Fibr. Cart.
FlG. 63. — Transverse section through the middle of the glans penis
of the ram. x 45.
Corp. Cav., corpus cavernosum ; Fibr. Cart., fibro-cartilage ; GL, erectile
tissue of glans ; Int., integument ; Ur., "urethra.
The penis in the male mammal is represented in the female
by the diminutive clitoris. This organ, however, is not
traversed by the urethra (at least in the majority of animals).
250 THE PHYSIOLOGY OF REPRODUCTION
On the other hand, the corpora cavernosa and the glans are
represented by homologous structures. The clitoris, like the
penis, contains very numerous sensory nerve endings l and under-
goes erection during sexual congress.
The relation between the clitoris and the uro-genital canal
is closer in some Mammals than in others. In some species
(e.g. the capybara among the Rodents, and Tupaia among
Insectivores) the clitoris is of considerable size, and is grooved
along its under surface in relation to the upper wall of the
urethra. In other animals (e.g. Arvicola, Talpa, and Stenops)
the groove on the under surface of the elongated clitoris is
converted by the coalescence of its margins into a tube, which
FIG. 64. — Distal end of bull's penis as seen from left side, showing glans and
urethral papilla representing vestigial filiform appendage. The prepuce
is folded back. About two-thirds natural size.
constitutes the urethral portion of the uro-genital canal.
Further, in the female of the spotted hyena (H. crocuta), the
whole of the uro-genital canal, beyond the apertures of the
ducts of Bartholini's glands, is prolonged forward to the ex-
tremity of the clitoris and terminates in a similar manner
to that of the urethra of the male. In this animal, therefore,
the vagina is completely absent, the os uteri opening directly
into the uro-genital canal, which is elongated and tubular in
form as in the male. A somewhat similar condition has been
known to occur abnormally in the human female.2
1 Worthmann,"Beitrage zur Kenntniss der Nervenausbreitung in Clitoris
und Vagina," Arch. f. Mikr. Anat., vol. Ixviii.
2 Watson (M.I, " The Homology of the Sexual Organs illustrated by Com-
parative Anatomy and Pathology," Jour, of Anat. and Phys., vol. xiv.,
1879.
MALE ACCESSORY REPRODUCTIVE ORGANS 251
THE MECHANISMS OF ERECTION, EJACULATION, AND
RETRACTION.
The erection of the penis is brought about mainly by_the^
dilatation of its blood-vessels. First of all the bulbous
(proximal) part of the organ increases in size, and then the
swelling extends throughout the cavernous bodies, and eventually
to the glans. If the penis is cut across when in a state of re-
laxation only a small quantity of venous blood exudes from the
wound ; but if the same operation is performed during erection,
the blood flow is enormously increased, while simultaneously
becoming bright and arterial in colour.1 Fran£ois-Franck,2
observed a corresponding rise in the arterial and venous tension.
He found also that the organ in the process of erection became
very considerably swollen in size before the increase in the
blood pressure had extended to the veins. Loven 3 showed
that the veins in the penis are traversed by five times as much
blood during erection as they are in a state of repose. The
same investigator found that, whereas the ordinary arterial
pressure in the penis is about half that of the carotid, during
erection it rose to three-fifths that of the carotid. The increase
in the amount of blood in the organ is accompanied by a rise of
temperature.4
There can be no doubt that the erection of the penis is
brought about partly through the contraction of the ischio-
cavernosus (or erector penis) and bulbo-cavernosus muscles,
certain of the fibres of which pass over the efferent vessels, and so
arrest the outward flow of blood.5 The result of this contraction
1 Eckhard, " Untersuchungen iiber d. Erektion d. Penis beim Hunde,"
Beitr, zur Anat. und Phys., vol. iii., Giessen, 1863.
2 Fran^ois-Franck, " Recherches sur 1'Innervation Vaso-motrice du Penis,"
Arch, de Phys., 1895.
3 Loven, Berichte iiber die Verhandlungen der Konigl. Sachs. Gesell. zu
Leipzig, vol. viii., 1866. Nikolsky, " Ein Beitrag zur Physiologic des Nervi
erigentes," Arch. f. Anat. u. Phys., Phys. Abth., 1879.
4 Retterer, Article on " Erection," in Richet's Dictionnaire de Physiologic,
vol. v., 1902.
5 De Graaf (Regner), De Virorum Organis Generationi Inservientibus,
Geneva, 1785. Giinther, Untersuchungen und Erfahrungen aus dem Gebiete
der Anatomic, vol. i., Hanover, 1837. Kobelt, DC VAppareil du Sens Genital
des Deux Sexes, Strasbourg, 1851. For further references, see Retterer, loc. cit.
252 THE PHYSIOLOGY OF REPRODUCTION
is, that whereas the blood can freely enter the dilated vascular
spaces of the penis, its exit is retarded, while this leads to a
further distension of the vessels, the venous outlets of which
become still more compressed.
Although the muscular mechanism of the penis unques-
tionably assists in the erection of that organ, it is equally clear
that it is incapable by itself of causing that phenomenon, since
erection cannot be induced by ligaturing the efferent veins.
Moreover, the penis can be made to erect in animals in which the
muscular mechanism has been paralysed by the injection of
curari, but the erection in such cases is incomplete.
It is stated also that the smooth or unstriated muscle fibres,
which are scattered throughout the trabecular framework of the
corpora, participate in the process of erection, but there has
been some disagreement as to the precise part they play.
Kdlliker 1 suggested that their action is temporarily inhibited,
and that the relaxation of the trabeculae, which consequently
follows, permits the vascular spaces to distend. According to
Valentin,2 these muscles contract, and in so doing cause a
dilatation of the walls of the vessels, which thereby increase in
volume. Langley and Anderson's observations, which support
Kolliker 's suggestion, are described below in giving an account
of the nervous mechanisms of erection and retraction.
It is obvious, however, that in those cases in which the penis
remains erected for a considerable time a constant circulation
must be maintained through both the afferent and the efferent
vessels of the organ.
In some animals (dog, cat, horse, hedgehog), but not in the
rabbit or Man, the penis possesses an accessory muscle. This is
called the retractor penis. It consists of a thin band of longi-
tudinally arranged, unstriated fibres, inserted at the attach-
ment of the prepuce, and continued backwards in the middle
line over the ventral surface of the corpus spongiosum to the
bulbous part of the urethra, where it divides into two halves
which separate on either side of the anus. Some of the fibres are
continuous with a portion of the bulbo-cavernosus of the same
side, while others are connected with the wall of the urethra.
1 Kolliker, Verhandl. der Wurzburger Phys. Med. Gesell., vol. ii., 1851.
2 Valentin, Lehrbuch der Physiologie, vol. ii., 1844.
MALE ACCESSORY REPRODUCTIVE ORGANS 253
When it contracts it causes a marked dorsal curvature of the
penis.1
Although the sexual orgasm is usually accompanied by a
high degree of mental excitement, it is essentially a reflex action,
and can take place when all connection with the brain is severed"
by transection of the spinal cord. It is generally believed that
the centre for erection lies in the lumbo-sacral region of the
cord.2 Numerous experiments have been recorded which prove
conclusively that it is not situated in the upper part of the cord
or in the brain. Thus, Goltz 3 showed that transection of the
spinal cord above the lumbar region did not destroy the reflex.
Brachet 4 also has recorded the occurrence of ejaculation under
a similar condition. According to Miiller,5 only the lower part
of the cord need be retained in order to preserve the erection
reflex, since this is still present after the complete destruction of
the cord in the whole of the lumbar and the upper part of the
sacral region. Miiller was able to induce erection in a dog,
which had undergone this operation, by rubbing the surface
of the penis.
It is known, however, that erection (and even ejaculation)
1 Langley and Anderson, " The Innervation of the Pelvic and Adjoining
Viscera: Part III. The External Generative Organs," Jour, of Phys., vol. xix.,
1895. The retractor muscle is remarkable for its sensitiveness to changes of
temperature, and at the same time for being unusually tenacious of life. It
can be cut out of the body and preserved in blood serum, in a cool place, for
days at a time, and afterwards, on warming, will relax and undergo spontaneous
contractions. At a temperature of 40° C. it is quite placid ; but, on cooling
slightly, it will shorten, and not infrequently enter into a series of slow
rhythmic contractions. If cooled to 15° C. it will contract to about one
quarter of its original length. (Sertoli, "Contribution h, la Physiologic
Ge"nerale des Muscles lisses," Arch. Ital. de Biol., vol. iii., 1883 ; Gruenhagen,
"Das Thermotonometer," Pfliiger's Arch., vol. xxxiii., 1884. See also
Fletcher, " Preliminary Note on the Motor and Inhibitory Nerve-Endings
in Smooth Muscle," Proc. Phys. Soc., Jour, of Phys., vol. xxii., 1898.)
a See Onuf, "Notes on the Arrangement and Function of the Cell
Groups in "the Sacral Eegion of the Spinal Cord," Jour, of Nervous and
Mental Diseases, 1899.
3 Goltz, " Ueber das Centrum der Erectionsnerven," Pfliiger's Arch.,
vol. vii., 1873. See also Goltz and Frensberg, "Ueber die Functionen des
Lendenmarks des Hundes," Pfliiger's Arch., vol. viii., 1874.
** Brachet, Recherches experimentales sur les Fonctions du Systeme Nerveux
Ganglionaire, Paris, 1839.
5 Miiller, " Klinische und Experimentelle Studien iiber die Innervation der
Blase," &c., Deutsche Zeitschr. f. Nervenheilk. , vol. xxi. , 1902.
THE PHYSIOLOGY OF REPRODUCTION
can also be induced voluntarily by stimuli conveyed from the
brain (i.e. by sexual emotion). It is interesting to note, there-
fore, that Budge l and Eckhard 2 were able to cause the penis to
erect by electrical stimulation of the cervical cord, the pons,
and the crura cerebri. The same result was obtained by Pussep
by exciting a definite region in the cerebral cortex. In this case
erection was followed by ejaculation.3
It is stated also that hanging and decapitation in Man
are sometimes followed by erection.4 According to Spina,5
who experimented on the guinea-pig, section of the spinal cord,
near the last costo- vertebral articulation, is invariably suc-
ceeded by erection and ejaculation.
There are certain facts which seem to show that the
higher nerve centres exercise an inhibitory influence over the
sexual processes. Thus, Retterer6 states that it is easier to
induce erection by external irritation in a dog whose spinal
cord has been cut through, than in a normal animal.
Eckhard 7 was the first to show that the penis in the dog
could be induced to erect experimentally by the stimulation of
certain nerves which he called the nervi erigentes. These nerves,
which are truly vaso-dilator, were found in the dog to arise from
the 1st and 2nd sacral nerves, and in some cases from the 3rd
sacral nerve also. Gaskell 8 showed that in the rabbit the
erector fibres leave the spinal cord by the anterior (and not by
the posterior) roots of the 2nd and 3rd sacral nerves. Morat 9 also
1 Budge, " Ueber das Centrum genitospinale des Nervus sympatheticus,"
Virchow's Archiv, vol. xv., 1858. 2 Eckhard, loc. cit.
3 Pussep, " Ueber die Gehirnzentren der Peniserektion und des
Samenergusses," Inaug.- Dissert., St. Petersburg, 1£02. Abstract in Le
Physiologiste Russe, vol. iii., 1904.
4 Gotz, ' tiber Erektion und Ejaculation bei Erhiingten," Inaug.-Diss.,
Berlin, 1898.
5 Spina, ' ' Experimentelle Beitrage zu der Lehre von der Erektion und
Ejaculation," Wiener Med. Blatter, 1897.
6 Retterer, Article " Erection," in Richet's Dictionnaire de Physiologic,
vol. v., Paris, 1902.
7 Eckhard, loc. cit.
8 Gaskell, " On the Structure, Distribution, and Function of the Nerves
which Innervate the Visceral and Vascular Systems," Jour, of Pkys.,
vol. vii., 1886.
9 Morat, " Les Nerfs Vaso-dilatateurs et la Loi de Majendie," Arch, de
Phys., 1890.
MALE ACCESSORY REPRODUCTIVE ORGANS 255
found that in the dog these fibres are contained only in the
anterior roots of the 1st and 2nd sacral nerves.
The corresponding parts in the female are similarly in-
nervated. Thus, Langley1 has described stimulation of the
sacral nerves in the vertebral canal of the rabbit as producing
dilatation and flushing of the vulva. These effects were most
marked on exciting the 3rd and 4th sacral nerves. The stimu-
lation of the 1st and 2nd sacral nerves, on the other hand,
generally produced contraction and pallor. Langley obtained
similar results in experiments on the male rabbit, the stimulation
of the sacral nerves causing either protrusion and flushing of the
penis, or else retraction and pallor.
Nikolski 2 had previously stated that, on stimulating the
anterior ramus of the nervus erigens (or the ramus from the
1st sacral) in the dog, he obtained a vaso-constrictor instead
of a vaso-dilator effect, thus differing from Eckhard and other
investigators.
Sherrington 3 found that in the male monkey excitation of
the 2nd and 3rd sacral nerves produced moderate erection, and
that of the 1st sacral only slight erection. In the female monkey
the effects of stimulating the 3rd sacral were usually greater
than in the case of the 2nd, while the 1st sacral produced no
certain effects. Similar results were observed in experimenting
on the cat, but in this animal stimulation of the 1st sacral nerve
appears to have had a more marked effect.
Fran9ois-Franck 4 found that the anterior ramus from the
1st sacral, was capable of causing both vaso-constriction and
vaso-dilatation. This investigator noticed further that both
effects could be produced by stimulating the hypogastric nerves,
but that the vaso-dilator action was more pronounced.
Budge 5 also described erector action from the hypogastrics
in the rabbit. Langley and Anderson,6 however, were unable
1 Langley, ''The Innervation of the Pelvic Viscera," Proc. Phya. Soc.,
Jour. ofPhys., vol. xii., 1891.
2 Nikolski, loc. cit.
3 Sherrington, " Notes on the Arrangement of some Motor Fibres in the
Lumbo-Sacral Plexus," Jour, of Phya., vol. xiii., 1892.
4 Francjois-Franck, loc. cit. 5 Budge, loc. cit.
6 Langley and Anderson, " The Innervation of the Pelvic and Adjoining
Viscera," Jour, of Phya., vol. xix., 1895.
256 THE PHYSIOLOGY OF REPRODUCTION
to confirm this statement, but they found that the hypogastrics
sometimes contained constrictor fibres for the external gene-
rative organs.
They state that they could discover no satisfactory evidence
of the presence of vaso-dilator fibres in any of the upper or
lumbar set of nerves. It would appear, therefore, that the
vaso-dilator function is probably confined to the lower or
sacral set of nerves.
Following Langley and Anderson's description, the fibres
from the sacral set of nerves may be divided into two groups
or classes, the visceral and the somatic. Stimulation of the
visceral fibres (which run in the nervi erigentes) produces dilator
effects on the vessels of the penis (and vulva), as already de-
scribed. It also causes inhibition of the unstriated muscles of
the penis, the retractor muscle of the penis (when present), and
the unstriped muscles of the vulva (in the female). The somatic
sacral nerves send motor branches to the ischio-cavernosus and
bulbo-cavernosus muscles, as well as to the constrictor urethrse
or deeper muscular stratum of the perineum. In the female
they innervate the erector clitoridis, which represents the ischio-
cavernosus, and the sphincter vaginae, which embraces the
lower end of the vagina, and is the homologue of the bulbo-
cavernosus. The sacral nerves, as far as Langley and Anderson l
were able to determine, send no visceral fibres by their somatic
branches.
The same investigators found that stimulation of the upper
or lumbar set of nerves produced strong contraction of the
vessels of the penis,2 as well as contraction of the retractor
muscle, and of the other unstriated muscles of the penis, prepuce,
and scrotum (dog, cat, and rabbit). The penis underwent
marked retraction as a result of the excitation. Stimulation of the
2nd lumbar nerves in the cat generally produced a slight but
distinct action on the external generative organs. The 3rd,
4th, and 5th lumbar nerves in many cases had a strong
action, but the 6th had no action. The 1st lumbar and 13th
thoracic were found to have a slight action. In the dog stimu-
1 Langley and Anderson, loc. cit.
2 Vaso-constrictor fibres for the penis were first found by Eckhard (loc. cit.)
in the nervus dorsalis penis.
MALE ACCESSORY REPRODUCTIVE ORGANS 257
lation of the 5th lumbar nerve had no effect upon the generative
organs, but the 1st lumbar was observed to have a distinct
action, and also the 13th and 12th thoracic. In the rabbit no
effect was produced by stimulating the 1st lumbar nerve. The
2nd lumbar had a slight action occasionally, but the 3rd, 4tE,
and 5th lumbar nerves always had an effect which was more or
less pronounced.
The fibres from the lumbar nerves run in the white rami
communicantes to the sympathetic chain, where they take two
routes, (a) The majority of the fibres take the course of the
pudic nerves (nervi pudendi). They follow the sympathetic
chain to the sacral ganglia, from which fibres are given off, and
these run in the grey rami communicantes to the sacral nerves.
Their further course is by way of the pudic nerves (i.e. in the
somatic branches), none apparently running in the nervi erigentes
(i.e. to the visceral branches), (b) The second of the courses
taken by the lumbar nerve fibres is that by the pelvic plexus.
Only a relatively small number, however, take this route.
Most of them run in the hypogastric nerves, but a few may join
the plexus from the lower lumbar or upper sacral sympathetic
chain, or from the aortic plexus. Of these latter, some may
join the first root of the nervus erigens, and proceed with it to
the pelvic plexus.1
It has already been mentioned that the clitoris in the female,
like the penis, undergoes erection during coitus. The same is
the case with the other parts of the vulva which contain erectile
tissue. The friction which is set up between these structures
and the glans of the penis causes a reflex discharge of motor
impulses in both the female and the male. In the female the
uterus undergoes a series of peristaltic contractions, by means
of which the semen is sucked into its cavity (see p. 180). More-
over, Bartholini's glands show an increased activity and pour
out a viscid secretion. In the male, the sexual impulses cul-
minate in the emission of the semen. This is brought about
by a series of muscular contractions, which probably begin in
the walls of the vasa efferentia and pass to the canal of the
epididymis, and thence along the vas deferens on either side.
The vesiculse seminales contract simultaneously, expelling their
1 Langley and Anderson, loc. cit.
R
258 THE PHYSIOLOGY OF REPRODUCTION
contents into the vasa, and the mixed fluid passes out through
the ejaculatory ducts into the prostatic portion of the urethra.
The prostatic muscles also contract, and probably assist in
forcing the semen along the urethra, while at the same time
expelling the secretion of the prostate glands. Entrance to the
bladder is prevented by the erection of the crista ure three, assisted
by the contraction of the sphincter of the bladder, as already
mentioned. The final discharge is brought about by the
rhythmical contractions of the bulbo-cavernosus and ischio-
cavernosus muscles, which have the effect of emptying the
canal from behind forwards, and so ejecting the semen, mixed
with the various glandular secretions, into the vaginal passage
of the female.
The innervation of the muscles of the penis has already been
described.
The secretory cells of Cowper's glands receive branches from
the pudic nerves.
The prostate is innervated by fibres coming both from the
nervi erigentes and from the hypogastric nerves. The former
are purely motor, whereas the latter are both motor and secretory.
Eckhard l found that stimulation of the nervi erigentes in the
dog caused the expulsion of the prostatic secretion into the
urethra. Loeb 2 obtained contraction of the prostatic vesicles
by excitation of the hypogastric nerves. Mislawsky and
Bormann 3 confirmed both these observations, and found also
that stimulation of the hypogastrics, while inducing the muscles
to contract, at the same time promoted secretory activity in the
glandular cells, the secretion continuing so long as the stimula-
tion was kept up.4 Fogge also states that he found hypogastric
stimulation to produce contraction of the prostatic muscles.5
1 Eckhard, loc. cit.
2 Loeb (A.), " Beitrage zur Bewegung des Samenleiters," Inaug. -Dissert.,
Giessen, 1866.
3 Mislawsky and Bormann, " Die Secretionsnerven der Prostata," Zentralbl.
f. Phys., vol. xii., 1898.
4 Timofeew has described end-bulbs in the prostate, testis, and other
male genital organs. Some of these are of a peculiar kind, and are in
connection with two nerve-fibres (" Zur Kenntnis der Nervenendigungen in
den Mannlichen Geschlechtsorganen der Sauger," Anat. Anz., vol. ix., 1894).
5 Fogge, " On the Innervation of the Urinary Passage in the Dog," Jour.
ofPhys., vol. xxviii. , 1902.
MALE ACCESSORY REPRODUCTIVE ORGANS 259
Akutsu 1 has shown that the vesiculse seminales in the guinea-
pig receive fibres (motor as well as secretory) by the hypogastric
nerves. The fibres leave the spinal cord in the 2nd, 3rd, and
4th lumbar nerves.
Budge 2 showed that it was possible to induce contraction oF
the vasa deferentia by stimulating the spinal cord at the level
of the 4th lumbar vertebra. He observed also that contraction
could be caused by stimulating one of the sympathetic ganglia,
apparently the inferior mesenteric.3
According to Remy,4 stimulation of a small ganglion situated
FIG. 65. — End-bulb in prostate. (After Timofeew, from Nagel.)
a, thick medullated nerve fibre ; b, fine medullated nerve fibre.
on the inferior vena cava at the level of the renal veins in the
guinea-pig produced a sudden ejaculation.
Loeb 5 states that he was able to induce contraction of the
vasa deferentia by stimulating the hypogastric nerves.
Langley 6 found that most of the efferent fibres for the vasa
deferentia traversed the sympathetic in the region of the 4th,
5th, and 6th lumbar ganglia, so that presumably they chiefly
arose from the 3rd, 4th, and 5th lumbar nerves. Sherrington 7
observed that in the macaque monkey (Macacus rhesus), the
1 Akutsu, " Beitrage zur Kenntniss der Innervation der Samenblase beim
Meerschweinchen," Pfliiger's Archiv, vol. xcvi., 1903.
2 Budge, loc. cit. 3 Langley and Anderson, loc. cit.
4 Remy, " Nerfs ejaculateurs," Jour, de I'Anat. et de la Phys., vol. xxii.,
886
5 Loeb, loc. cit. 6 Langley, loc. cit.
7 Sherrington, loc. cit.
260 THE PHYSIOLOGY OF REPRODUCTION
2nd and 3rd lumbar nerves, and in the cat, the 3rd and 4th
lumbars, contained motor fibres for the vasa deferentia. The
fibres giving this result could be found outside the spinal cord
in the geni to-crural nerve. The contraction of the vasa was
of a slow and peristaltic kind, and did not cease immediately
the stimulus was withdrawn.1
Langley and Anderson, as a result of an extensive series of
experiments, conclude that the internal generative organs of the
cat and rabbit are supplied by fibres running out by the anterior
roots of the 3rd, 4th, and 5th lumbar nerves, and sometimes
also the 2nd. These fibres pass through the sympathetic to the
inferior mesenteric ganglia, and continue their course by the
hypogastric nerves. Stimulation of these fibres in the cat and
the rabbit caused strong contraction of the whole musculature
of the vasa deferentia and uterus masculinus (which Langley
and Anderson regard as the physiological homologue of the
vesiculse seminales in these animals). The vas deferens in con-
tracting was observed to become from one to three centimetres
shorter, so that there could be no doubt that the longitudinal
muscular coat took part in the process. The contraction was
strong enough to cause emission of semen from the aperture of
the penis. It would appear, therefore, that ejaculation occurred
without erection. In the dog, in which the longitudinal muscle
layer is not well developed, the contraction of the vas deferens,
on excitation of the upper lumbar nerves, was not nearly so
pronounced.
Langley and Anderson found that stimulation of the sacral
nerves had no effect on the internal generative organs. These
1 There has been some disagreement as to whether the vas deferens under-
goes true peristaltic movement. According to Budge (loc. cit. ) this does occur
in the rabbit and cat. Tick confirmed Budge for these animals (" Ueber das
Vas deferens," Mailer's Archiv, 1856), but found no peristalsis in the dog
(c/. Langley and Anderson for the dog). On the other hand, Loeb (loc. cit.)
could discern no peristaltic movement in the vas deferens of the rabbit,
but only a powerful contraction. Nagel, who has more recently investigated
the question, states that the vas deferens in the rabbit does not undergo a
true peristaltic movement, but a simple quick contraction which suffices for
the emptying the tube (" Contractilitat und Rarzburkeit des Samenleiters,"
Verhandl. d. Phys. Gesell. zu Berlin ; Arch.f. Anat. u. Phys., Phys. Abth.,
1905, Suppl. See also Nagel, Handbuch der Phys. des Menschen, vol. ii.,
Braunschweig, 1906).
MALE ACCESSORY REPRODUCTIVE ORGANS 261
are innervated exclusively from the lumbar nerves, as above
described.1
In view of the facts which have been related, it would appear
that ejaculation is a reflex act of some complexity involving
v. D.
IV.
FIG. 66. — Diagram illustrating innervation of internal genital organs of
male cat. (From Nagel. )
H., hypogastric nerve ; Ur., ureter; V. D., vas deferens ; II. III. IV.,
branches arising from 2nd, 3rd, and 4th lumbar nerves.
more than one centre in the spinal cord. The centre for the
final expulsion of the semen must be the same as that for erec-
tion, since the muscular mechanisms concerned are to a large
extent identical in each case. The centre presiding over the
internal generative organs is apparently in the lumbar spinal
1 Langley and Anderson, loc. cit.
262 THE PHYSIOLOGY OF REPRODUCTION
cord. As akeady mentioned, Bracket observed ejaculation
after all connection with the higher centres had been cut off.
The centripetal nerves for the ejaculatory reflex are the sensory
nerves of the penis, the stimulation of the glans being particu-
larly effective.1
Erection has been observed to occur in animals which were
castrated late in life, sexual desire in such cases being to some
extent retained. It has been shown, however, that erection
cannot be induced experimentally in animals which have been
castrated prior to puberty ; or, at any rate, that it is far more
difficult to cause erection in such animals. Thus, in three
experiments carried out by the writer, in conjunction with
Professor Sutherland Simpson,2 it was found impossible to induce
erection by stimulating the nervi erigentes in three cats which
were castrated when about half grown and afterwards allowed
to reach their full size. It is possible, therefore, that in such
animals the muscular apparatus of the penis fails to develop
sufficiently to admit of erection occurring, but it would seem
unlikely that the nervous mechanism is impaired. If erection
is due mainly to an inhibition of the vaso-motors of the penis,
as is ordinarily supposed, there would seem to be no theoretical
reason why it should not be possible to bring about that process
experimentally in castrated animals. It is conceivable, there-
fore, that the process of erection is after all a more complex
phenomenon than is generally believed, but our experiments
throw no further light on the mechanism of that process.
1 For further references to the literature of the nervous mechanism of
erection and ejaculation, see Bechterew, Die Funktionen der Nervencentra,
Weinberg's German Translation, vol. i., Jena, 1908.
2 Simpson and Marshall, "On the Effect of Stimulating the Nervi
Erigentes in Castrated Animals," Quar. Jour. Exper. Phys., vol. i., 1908.
CHAPTER VIII1
THE BIOCHEMISTRY OF THE SEXUAL ORGANS
" Nous sommes dans un de ces chateaux des legendes allemandes oii les
murs sont formes de milliers de fioles qui contiennent les ames des
hommes qui vont naitre. Nous sommes dans le sejour de la vie qui
precede la vie." — MAETERLINCK, La Vie des Abeilles.
THE FEMALE GENERATIVE ORGANS
Mammals
IN Mammals very little is known concerning the chemistry of
the female generative organs. The difficulty experienced in
obtaining material has rendered impossible a chemical investiga-
tion of the ovum itself. The fluid contained in the Graafian
follicles of the cow is stated to be of a serous nature. From
the corpora lutea of the same animal amorphous and crystalline
pigments have been isolated, both of which belong to the class
of substances called lipochromes or luteins.2 These pigments
are also found in other sites, e.g. in adipose tissue, in serum, in
the retina, and in milk. Similar substances have been isolated
from plants, e.g. the crystalline caroten which constitutes the
colouring matter of carrots and tomatoes. The luteins are not
related to blood pigment, and although hsematoidin may be found
in corpora lutea, especially when they are fresh, the existence of
the luteins appears to be quite independent of the presence of
blood pigments. The luteins contain carbon, hydrogen, and
oxygen, and have a yellowish or reddish colour. Exposed to
light they undergo oxidation. They are soluble in alcohol, ether,
and chloroform, and in that respect resemble fats, from which
they differ, however, in their resistance towards alkalies. With
1 By William Cramer.
2 Piccolo and Lieben, " Studi nel corpo luteo della vacca," Oiorn. sc.
natur. ed econ., vol. ii., 1866. Kiihne and Ayres, " On the Stable Colours
of the Ketina," Journal of Physiology, vol. i., 1878.
264 THE PHYSIOLOGY OF REPRODUCTION
strong nitric acid and sulphuric acid they give a blue colour.
Their solutions in alcohol, ether, or chloroform are further
characterised by the absorption-spectrum,1 which shows two
bands in the blue part of the spectrum (between the lines F
and G).
Observations concerning the chemistry of human ovaries have
been made chiefly in certain pathological conditions of these
organs. Various protein substances have been isolated from
the fluid contents of ovarian cysts. In the case of cysts due
to a dilatation of the Graafian follicles the contents were found
to be identical with other serous liquids. From cystic tumours
of the ovaries, the contents of which may be either watery or
gelatinous, a number of protein compounds have been isolated,
which, on hydrolysis, all yield a considerable quantity of a re-
ducing substance — glucosamine — and therefore belong to the
group of glycoproteins. Hammarsten 2 isolated a substance,
called by him Pseudomucin, which did not coagulate on heating
and was not precipitated by acetic acid. On hydrolysis it yielded
30 per cent, glucosamine. Pfannenstiel 3 isolated from ovarian
colloid another mucoid substance, Pseudomucin /3, a gelatinous
mass which was insoluble in acetic acid and water, but was
dissolved by dilute alkali. These substances are formed by the
activity of the cells lining the cysts.
Birds
Our knowledge of the chemistry of the ovum is derived
almost entirely from investigations on the hen's egg. The
average weight of an egg is 40-60 grm., half of this being the
weight of the white of the egg, while the yolk weighs 12-18
grm. and the shell 5-8 grm.
The egg-shell contains chiefly calcium carbonate. During
development the egg-shell loses calcium, which goes to the
building up of the structures of the developing embryo.4 In
1 Thudichum, " Uber das Lutein und die Spektren gelbgefarbter organ-
ischer Substanzen," Centralblatt f. d. med. Wissenschaft, 1869, vol. vii.
2 Hammarsten, " Metalbumin und Paralbumin," Zeitschr. f. physiol.
Chemie, vol. vi., 1882.
3 Pfannenstiel, " Uber die Pseudomucine der cvstischen Ovarienge-
schwiilste," Arch. f. Gyncekologie, vol. xxxviii.
4 Vaughan, "Estimation of Lime in the Shell and in the Interior of the
Egg before and after Incubation," Journal of Physiology, vol. i., 1878.
BIOCHEMISTRY OF THE SEXUAL ORGANS 265
some species the shell is coloured by pigments, which are pro-
bably derivatives of the bile pigments.1
The shell membrane consists of a substance belonging to the
group of the keratins. It is very rich in sulphur (about
4 per cent. S.), and, on hydrolysis, yields a relatively large
amount of cystin (see p. 276).
The chief constituents of the white and the yolk of the egg
are water, proteins, fats, and phosphorised fats, while carbo-
hydrates as such are almost entirely absent.
The proportion in which these constituents are present in
the white and in the yolk of the egg differs, as will be seen from
the following table giving the total composition of both these
parts.
White of Egg. Yolk of Egg.
Per Cent. Per Cent.
Water ....
85-88
47-19
Protein ....
13-0
15-63
Fat .
0-3
22-84
Phosphorised fat, calculated
as Lecithin
> trace
10-72
Cholesterin
V
1-75
Reducing sugar
)5
trace
Inorganic salts .
07
0-96
Ash . . .
4-61
2-91
Another important difference in the composition of the
white and the yolk of the egg is to be found in the relative
quantities of the inorganic constituents as they are present in
the dry residue,2 both as in organic salts and inorganic com-
bination.
100 parts of Dry
Residue of * K2O.
White of egg . 1-44
Contain —
Na20. -CaO. MgO. Fe2O3. P2O5. Cl.
1-45 0-13 0-13 O'OO 0-20 1'32
Yolk of egg . 0-27
0-17 0-38 0-06 0-024 T90 0'35
1 Krukenberg, " Farbstoffe der Vogeleierschalen," Verhandlungen d.
Phys. Med. Gesellschaft, Wiirzburg, vol. xvii., 1883.
2 Bunge, " Der Kalk und Eisengehalt unserer Nahrung," Zeitschrift f.
Biologie, vol. xlv., 1904, p. 532.
266 THE PHYSIOLOGY OF REPRODUCTION
It will be seen that the yolk is distinguished by the presence
of iron which is almost completely absent in the white, and by
its richness in phosphorus. Although the percentage of iron
present in the yolk is very small, it is nevertheless greater than
in almost any other animal or vegetable food-stuff.
As a rule the proportions in which the inorganic elements
are present are given in terms of percentages of the ash. Such
a table,1 which perhaps brings out more clearly the difference
between the white and the yolk of the egg, may be given here : —
100 parts of the Contain —
Ash of K20. Na2O. CaO. MgO. Fe2O3. P205. Si02. Cl.
White of egg 31'41 31'57 2'78 2'79 0'57 4'71 1'06 28'82
Yolk of egg. 9-29 5'87 13'04 2'13 1'65 65'46 0'86 1'95
There are, of course, slight variations between different eggs
in the amount of mineral constituents present in the ash. It is
possible that there are such variations even in the eggs laid by
one and the same bird at different periods. Systematic investi-
gations on this point have been made only with reference to
the iron. These observations show that more iron is present
in eggs laid in spring than in eggs laid by the same bird
in autumn, the amounts varying from 0.0129 per cent. Fe203 to
0'0086 per cent. Fe203, the maximum found being 0'0167 per
cent. Fe203. (The percentage is calculated for the dried yolk.)
This fact probably explains the very exaggerated statements which
have been made concerning the production of eggs rich in iron
by keeping hens on a diet rich in iron. The careful observations
of Hartung 2 show that there is indeed a distinct effect produced
by such a diet, provided that it is given over a prolonged period
— two months or more. But the effect of such a diet is limited,
and does not go beyond the physiological maximum. The
percentage of iron present in eggs laid under these conditions
remains fairly constant, and is about equal to the maximum
found under normal conditions, namely 0*0165 per cent. Fe203, so
that the seasonal diminution which normally appears is prevented.
1 Albu and Neuberg, Physiologic und Pathologic des Mineralstoffwechsels
Berlin, 1906, p. 241.
2 Hartung, "Der Eisengehalt des Hxihnereies," Zeitschrift fur Biologic,
vol. xliii., 1902.
BIOCHEMISTRY OF THE SEXUAL ORGANS 267
The phosphoric acid constitutes more than half of the ash
of the yolk, and it is interesting to note that both the phosphorus
and the iron which are destined to enter into the composition
of some of the most important constituents of the cell, sjich
as nucleoproteins, haemoglobin, lipoids, &c., are already present
in organic combination. The phosphorus is contained in the
phosphorised fats, which constitute about 11 per cent, of the
yolk, and partly in the phosphoprotein vitellin, which also
contains iron.
The phosphorised fats are obtained by extracting the yolk,
which has previously been freed from water, with cold ether,
and precipitating the ethereal extracts with acetone. The
precipitate contains the phosphorised fats, while the acetone
solution contains the cholesterin which has been extracted
together with the phosphorised fats. After all the ether-soluble
phosphorised fats have been removed by the ether, further
extraction with cold alcohol will remove other phosphorised
fats from the yolk.
The precipitate obtained from the ethereal extract by
acetone has often been called lecithin, the name given to the
simplest and best-known phosphorised fat. But the recent
work of Erlandsen,1 and of Thierf elder and Stern,2 has shown,
what in the case of nervous tissue had been recognised long ago
by Gramgee and by Thudichum, that there are a great number
of phosphorised fats very similar to lecithin and very difficult
to separate from each other. These substances, accompanied
always by cholesterin, are widely distributed through the
organic world. In fact they are present in every cell, and in
almost every animal fluid. This fact alone is sufficient to in-
dicate that the phosphorised fats and cholesterin must fulfil
an important function in the life of the cell.
What this function is has not yet been clearly recognised.
We know that anaesthetics such as chloroform, and toxins
such as snake-venom, exert their action on the cell by virtue of
the power of the phosphorised fats to absorb these substances.
1 Erlandsen, " Untersuchungen uber die lecithinartigen Substanzen des
Herzmuskels," Zeitschrift f. physiol. Chemie, vol. li. , 1906.
2 Thierfelder and Stern, " Uber die Phosphatide des Eigelbs," Zeitschrift
f. physiol. Chemie, vol. liii., 1907.
THE PHYSIOLOGY OF REPRODUCTION
One may therefore venture the suggestion that lecithin and its
allies have a similar function with regard to other substances
affecting the life of the cell under normal conditions. Some
experiments of the writer,1 carried out in 1908, suggest that
these phosphorised fats may act as oxygen-carriers, and that
they may thus fulfil an important function in cell-respiration.
A similar view has been put forward recently on purely
theoretical grounds by Mansfeld.2
However that may be, there can be little doubt that in
the egg which contains an exceptionally large amount of phos-
phorised fats these substances have to fulfil a different function.
Phosphorus enters into the composition of many cell consti-
tuents, for instance, the complex protein substances found
in the nuclei of cells, the so-called nucleoproteins, so that
the assimilation of phosphorus is an important factor in
the growth of an organism. Feeding experiments on Man
and on animals have made it probable that phosphorus in
organic combinations is better assimilated than phosphorus
which is given in the form of inorganic phosphates. In birds
the yolk of the egg fulfils a function similar to that of the milk
in Mammals ; both supply the offspring with the material
necessary for its growth. We thus find that both the yolk
and the milk are not only rich in phosphorus, but that most of the
phosphorus is present in organic combination, as casein and
nuclein in the latter, and as vitellin and phosphorised fats in
the former.
We also find that during incubation the vitellin disappears
and the phosphorised fats diminish, so that, at the twentieth
day, their quantity is reduced by one half.3 It is, of course,
1 Unpublished observations. It was found that watery emulsions of egg-
lecithin absorbed much more oxygen than water alone or watery solutions of
proteins, and that such a lecithin-emulsion sometimes greatly accelerated
the oxidation of hydriodic acid by the oxygen of the air. The results ob-
tained were, however, very variable.
2 Mansfeld, " Narkoseund Sauerstoff mangel, " Pfliiger's Archiv, vol. cxxix.,
1909.
3 Merconitzki, " Die quantitativen Veranderungen des Lecithins im
enstehenden Organismus," Russky Wratsch, 1907, quoted from Biochemisches
Centralblatt, vol. vi., 1907. Plimmer and Scott, "The Transformations in
the Phosphorus Compounds in the Hen's Egg during Development," Jour, of
Physiology, vol. xxxviii., 1909.
BIOCHEMISTRY OF THE SEXUAL ORGANS 269
clear that the formation of nucleoproteins cannot account for
this enormous consumption of phosphorised fats. Some of these
substances reappear in the embryo. A proportion of them
contributes to the formation of bones, which contain a con--
siderable amount of inorganic phosphates. Part reappears in
the foetal tissues as phosphorised fats, especially in the nervous
tissue, which is very rich in these substances. That portion of
the phosphorised fats which is transformed into inorganic
phosphates, may at the same time fulfil another very im-
portant function by the oxidation of the fat group in their
molecule. It will be shown below that the development of
the embryo is intimately associated with, and perhaps de-
pendent upon, the transformation of chemical energy into heat.
This transformation is brought about by the oxidation of
certain organic substances, which are different in the different
classes of Vertebrates. It will be shown also that in birds the
chemical energy is furnished by fats, and it is very probable that
the phosphorised fats furnish at the same time material for
the formation of the tissues of the embryo and fat as a source of
chemical energy.
It is interesting to note that a similar double function has
been assigned to glycogen in the case of the developing rabbit.1
Of the cholesterin about one- third disappears during incubation.
The phosphorus which enters into the composition of nucleo-
protein is bound up therein in the form of phosphoric acid,
combined with purine bases and pentoses (see p. 294). Neither
nucleoprotein nor pentoses are present in the fresh egg, and
purine bases are present only in very small amounts. The fact
that during development these substances rapidly increase in
amount, indicates therefore that a synthesis of nucleoprotein
from the reserve material of the egg (proteins and phosphorised
fats) takes place during development. The purine bases
found in the embryo are essentially the same as those found
in the adult organism.2
1 Lochhead and Cramer, " The Glycogenic Changes in the Placenta and
Foetus of the Pregnant Rabbit," Proc. Roy. Soc., Series B., vol. Ixxx., 1908.
2 Kossel, " Weitere Beitrage zur Chemie des Zellkernes," Zeitschrift fur
Physiologische Chemie, vol. x., 1886. Mendel and Leavenworth, "Chemical
Studies on Growth: VI. Changes in the Purine- Pentose- and Cholesterol-Content
of the Developing Egg," American Journal of Physiology, vol. xxi., 1898.
270 THE PHYSIOLOGY OF REPRODUCTION
Of the phosphorised fats of the yolk, lecithin is the simplest
and best-known representative. Like all fats, it is an ether
compound of glycerine and fatty acids, such as stearic, palmitic,
and oleic acid, and is, like all fats, soluble in alcohol and
ether. With water it swells up and forms a colloidal solution.
It is distinguished by the presence in its molecule of one molecule
of phosphoric acid to which one molecule of an organic nitro-
genous base, choline, is attached. If boiled with baryta water
it is decomposed into glycerophosphoric acid, fatty acids, and
choline. Lecithin forms loose compounds with proteins, the
so-called lecithalbumins, of which vitellin is probably one.
Vitellin is an ill-defined compound between lecithin and a
protein substance which itself contains about 1 per cent,
phosphorus. It is insoluble in water, but soluble in dilute
solutions of neutral salts, behaving in that respect like a globulin.
On peptic digestion a pseudonuclein, rich in phosphorus, is
formed from the protein part of vitellin. This pseudonuclein
contains also a relatively large amount of iron in organic com-
bination, and it is this substance which is responsible for the
presence of iron in the yolk of the egg. According to Bunge,1
this substance plays an important part in the formation of
haemoglobin in the chick. It is the precursor of haemoglobin,
and has, therefore, been called by him haematogen. It contains
5- 19 per cent. P., and 0*29 per cent. Fe. Recently Plimmer 2
has isolated from egg-yolk another protein, livetin, soluble
in water and containing (H per cent, phosphorus.
Two different fats have been isolated from the yolk — the
one solid, rich in palmitic acid ; the other fluid, containing equal
parts of palmitic and oleic acids. A small amount of stearic
acid is also present in both fats. The composition of the fat is
influenced by the food, the fat of the food passing into the yolk
in the same kind of way as it passes into the fat deposits of the
adult organism.3
The food has also an influence upon the colour of the yolk,
1 Bunge, " tiber die Assimilation des Eisens," Zeitschr. f. physiolog
Chemie, 1884, vol. ix.
2 Aders Plimmer, "The Proteins of Egg-Yolk," Journal Chemical Soc.,
1908.
3 Henriques and Hansen, " Uber den Ubergang des Nahrungsfettes in
das Hiihnerei," Skandin. Arch. f. Physiologic, vol. xiv., 1903.
BIOCHEMISTRY OF THE SEXUAL ORGANS 271
which is due to luteins. Feeding with grains produces a light
yellow yolk, a dark yellow yolk results if grass and herbs are
given, while feeding with worms leads to the production of an
even darker reddish yolk. What the changes are in the colour-
ing matter of the yolk has not yet been ascertained.1
During the development of the chick a considerable portion
of the fat disappears. In other words, a certain amount of
chemical energy, which in the fresh egg is present in the form of
fat, disappears. Liebermann 2 has shown, for instance, that of 5'4
grm. of fat present in a fresh egg only 2 '7 grm. can be recovered
when the chick is hatched. The fate of the chemical energy
which has thus disappeared has been accounted for completely
by the observations of Bohr and Hasselbalch,3 which are the
most exact and comprehensive investigations on the subject
of the metabolism of the embryo.
They showed that the respiratory quotient of the developing
egg — that is, the ratio of the amount of C02 excreted to the
amount of 02 absorbed — is 0*71. Such a quotient indicates the
oxidation of fat. From the amount of C02 excreted during a
given period it is possible to calculate the amount of fat oxidised
during that period. Under ordinary conditions the oxidation
of fat produces heat which can be determined experimentally.
By calculating from the amount of fat oxidised during de-
velopment the amount of heat which would be generated under
ordinary conditions, and by actually determining at the same
time the amount of heat given off by the developing egg, Bohr
and Hasselbalch found during a period of twelve days :—
The amount of heat calculated from the amount of
fat oxidised 12-11 Gal
The amount of heat actually given off ... 12-16 Cal.
This remarkable agreement in so complicated an experiment
—which is a triumph of the experimental skill of the observers
1 For the morphological distribution of the constituents of the yolk, see
Waldeyer, " Die Geschlechtszellen," in Hertwig's Handbuch der Entwicklungs-
lehre der Wirbeltiere, vol. i., Jena, 1903.
2 Liebermann, " Embryochemische Untersuchungen," Pflilger's Archiv,
vol. xliii., 1888.
3 Bohr and Hasselbalch, " Uber die Warmeproduktion und den Stoffwechsel
des Embryo," Skandinavisches Arch. f. Physiologic, vol. xiv., 1903.
272 THE PHYSIOLOGY OF REPRODUCTION
— shows clearly that fat is the almost exclusive source of the
chemical energy which is used up during development. Another
very important conclusion can be drawn from these observa-
tions, namely, that all the chemical energy which disappears
during development reappears in the form of heat. None is
transformed in an unknown way into energy of a different kind,
or transferred to the developing embryo.
The intensity of the metabolic changes which take place during
development, and which can be expressed by the amount of C02
excreted, is very great.1 Calculated for the same unit of weight
of the animal, it is as great in the embryo as it is in the adult
animal, and may even exceed it. This is the case not only in birds,
but also in Mammals. These changes are intimately bound up
with the development of the embryo. Exposure to cold, which
delays development, also diminishes the excretion of carbonic
acid.2 Experiments on the eggs of cold-blooded animals 3 show
that those conditions which favour development, such as high
temperature, also lead to an increase in the C02 excretion.
The same problem has been attacked in a different way by
Tangl.4 He determined, by means of a calorimeter, the heat
produced by the combustion of eggs at different stages of their
development. There is a gradual diminution of the caloric
value as development goes on, indicating that chemical energy
is used up in the process of development. In the case
of the chick the difference between the caloric value of the
fresh egg and that of the developed chicken is 16 calories.
These 16 calories represent the chemical energy which has been
used up for what Tangl calls the " work of development."
But since Bohr's work has shown that the chemical
energy which disappears during development is completely
transformed into heat, it would be better to replace the
1 Bohr and Hasselbalch, " Uber die Kohlensaureproduktion des Huhner-
embryos," Skandinav. Arch. f. Physiologic, vol. x., 1900.
2 Pembrey, " On the Response of the Chick, before and after Hatching,
to Changes in External Temperature," Journal of Physiology, vol. xxvii.,
1894.
3 Bohr, " Uber den respiratorischen Stoffwechsel beim Embryo kaltbliitiger
Tiere," Skandinav. Arch. f. Physiologic, vol. xv., 1904.
4 Tangl, " Beitrage zur Energetik der Ontogenese : I. Die Entwicklungs-
arbeit im Vogelei," Pfluger's Archiv, vol. xciii., 1903 ; vol. cxi., 1908.
BIOCHEMISTRY OF THE SEXUAL ORGANS 273
term " work of development " by the term " energy of
development.
The nature of the substances which by their oxidation
furnish the " energy of development " is different in the
different classes of animals. In birds it is furnished, as we
have seen, by the oxidation of fats, and possibly also of the
fat group of phosphorised fats. In Mammals in which de-
velopment proceeds in utero, and there is a constant exchange
of material between the mother and the foetus, the investigation
of these problems is more difficult, owing to the complexity of
the conditions. Investigations on the respiratory quotient of
the embryo in pregnant guinea-pigs and rabbits 1 indicate that
there is an oxidation of carbohydrate material, and systematic
chemical investigations of the placenta and foetus of pregnant
rabbits 2 have shown that there is a constant and regular dis-
appearance of glycogen from the placenta, which reappears
only partly as such in the embryonic tissues. It can there-
fore be concluded that in these animals glycogen furnishes
at least part of the " energy of development/' But it is
doubtful whether this conclusion can be applied to all the
Mammals, since, in the case of the cow and of the sheep, for
instance, very little glycogen is found in the placenta.
In reptiles 3 also the chemical energy used up during de-
velopment is furnished mainly by carbohydrates.
Similar observations have been made on the eggs of fishes,4
where the energy of development was found to be very small.
In all these cases the chemical energy used up in the
process of development has been found to be furnished either
by fats or by carbohydrates. No conclusive evidence has as
yet been obtained that the store of nitrogenous substances is
used for that purpose.
1 Bohr, " Der respiratorische Stoffwechsel des Saugethierembryos," SJcan-
dinai\ Arch. f. Physiologic, vol. x., 1900.
2 Lochhead and Cramer, " The Glycogenic Changes in the Placenta and
Foetus of the Pregnant Rabbit," Proc. Roy. Soc., Series B., vol. Ixxx., 1908,
p. 263.
3 Bohr, " liber den respiratorischen Stoffwechsel beim Embryo kaltblutiger
Tiere," loc. cit.
4 Tangl and Farkas, " Beitrage zur Kenntniss der Ontogenese : IV. liber
den Stoff u. Energieumsatz im bebriiteten Forellenei," Pfliiger's Archiv, vol.
civ., 1904.
274 THE PHYSIOLOGY OF REPRODUCTION
Liebermann records a loss of nitrogenous substances in his
analysis of hens' eggs at various stages of development ; but as
Hasselbalch l pointed out, this loss is accounted for by the egg-
membrane, which is left behind when the chick is hatched, and
which was not included in Liebermann's analysis.
Reference has already been made to nitrogenous consti-
tuents of the yolk : the two phosphoproteins vitellin and live tin.
The other protein substances of the white of the egg can be
distinguished according to their reactions as albumens, globulins,
and a substance behaving like a peptone in so far as it is not
coagulated by heat and not precipitated by ammonium sulphate or
by hydrochloric and acetic acids. According to the investiga-
tions of Morner,2 this substance is a true glucoprotein and belongs
to the mucoid substances. It has, therefore, received the name
Ovomucoid. On boiling with hydrochloric acid it yields 34 per
cent, of glucosamine.3 The amount of ovomucoid present in the
white of the egg is about 10 per cent, of the proteins ; 6 per
cent, of the proteins belong to the globulin group, the remainder
being the albumens. All the proteins of the white of the egg,
not only the ovomucoid, are exceptionally rich in the carbo-
hydrate radicle, and on boiling with dilute hydrochloric acid
yield considerable quantities of glucosamine. The albumens
and globulins contain about 10 per cent, of glucosamine. This
explains perhaps the almost complete absence of carbohydrates
in the egg. It acquires further significance from the fact that
the developing tissues of the embryo are very rich in mucin, a
protein containing considerable quantities of glucosamine.
The globulin fraction of the egg-white has not yet been
studied in detail. It is probable that it is a mixture of several
globulins.
The investigation of the albumen fraction has been greatly
facilitated by the work of Hofmeister 4 and Hopkins,5 which
1 Hasselbalch, " Uber den respiratorischen Stoffwechsel des Hiihner-
embryos," Slcandinav. Arch. f. Physiologic, vol. x., 1900.
2 Morner, " Uber die im Hiihnereiweiss in reichlicher Menge vorkonimende
Mucinsubstanz," Zeitschr. f. physiol. Chemie, vol. xviii.
3 Quoted from Ergebnisse der Physiologic, vol. i. , Part I.
4 Hofmeister, " Uber Kry stall isation des Eialbumins," Zeitschrift fur
physiolog. Chemie, vol. xiv., 1890, and vol. xvi., 1892.
5 Hopkins and Pinkus, " Observations on the Crystallisation of Proteids,"
Journal of Physiology, vol. xxiii., 1898.
BIOCHEMISTRY OF THE SEXUAL ORGANS 275
has made it possible to obtain part of the albumen fraction in a
crystallised form. In this way Osborne and Campbell 1 have
isolated two different albumens, the crystallisable " ovalbumen "
and the non-crystallisable " conalbumen." Possibly even these
two substances are mixtures of albumens, for Bondzinski and
Zoja 2 claim to have isolated from the crystallisable ovalbumen
several albumens by means of fractionate crystallisation.
Crystalline egg albumen contains 0*13 per cent, phosphorus,3 and
is therefore another source of phosphorus in organic combination.
The white of the eggs of some Insessores has the peculiar
property of forming a transparent fluorescent jelly when it is
coagulated by heat.4 The name " Tata-eggwhite," has been
given to this substance. This phenomenon is probably due to the
presence of a relatively large amount of basic salts in the white of
the egg, since the white of a hen's egg will also coagulate to a
transparent jelly if the egg has been kept for a few days in 10
per cent, caustic potash.
Further insight into the composition of some of the proteins
of the egg has been gained by means of the methods devised
within recent years by E. Fischer and by Kossel, for the study of
the constitution of the protein substances. By boiling with
hydrochloric acid the proteins are split into the constituent
amino acids and diamino acids, which are then determined as
nearly quantitatively as possible.5
In the results given in tabular form on p. 276, the figures
represent percentages, those under " total " indicating the per-
centage recovered in the form of amino acids or diamino acids.
The absence of any one constituent is indicated by 0, the presence
without quantitative estimation by + , while — indicates that
1 Osborne and Campbell, Journ. Americ. Chem. Soc., vol. xxii., 1900.
2 Bondzinski and Zoja, " fiber die fraktionierte Krystallisation des
Eieralbumins," Zeitschrift f. phys. Chemie, vol. xix., 1894.
3 Willcock and Hardy, " Preliminary Note upon the Presence of Phosphorus
in Crystalline Egg Albumin," Proc. Cambridge Philosophical Soc., 1907.
4 Tarchanoff, " Uberdie Verschiedenheiten des Eiereiweisses beibefiedert
geborenen (Nestfluchten) und bei nakt geborenen (Nesthocker) Vogeln,"
Pfliiger's Archiv, vol. xxxi., 1883. Tarchanoff, " Uber Hiihnereier mit
durchsichtigem Eiweiss," Pjluger's Archiv, vol. xxxix. , 1883.
5 For fuller reference see Plimmer, The Chemical Constitution of the
Proteins, London, 1908, in the series of Monographs on Biochemistry ; and
Abderhalden, Lehrbuch der Physiologischen Chemie, 2 Auflage, 1909.
276 THE PHYSIOLOGY OF REPRODUCTION
investigations as to the presence or absence of a particular
constituent have not been made.
Egg Albumen
(Abderhalden
and Pregl).
Vitellin
(Hughounenq).
Keratin from
Egg Membrane
(Abderhalden
and Ebstein).
Per Cent.
Per Cent.
Per Cent.
Glycine .
0
<0'5
3-9
Alaniue .
2-1
<0'5
3-5
Valirie .
—
1-5
1-1
Leucine .
6-1
6-8
7-4
Phenylalanine
4-4
0-7
-
Tyrosine
1-1
2-0
-
Serine .
—
<0'5
-
('ystine .
0-3
-
7-6
Proline .
2-3
<0'5
4-0
Oxyproline
—
-
_
Aspartic acid
1-5
0-7
1-1
Glutamic acid
8'0
1-0
8-1
Tryptophane .
+
-
-
-P.- . f Arginine
2-15
1-0
—
DiammoJ LV8jne
2-14
1-2
_
CSt lllistidine
—
2-1
—
Total .
30-1
19-0
367
With regard to the question of the presence of ferments and
their significance we are on very difficult ground. We must
here clearly distinguish between endo -enzymes and secreted
enzymes. The endo -enzymes comprise all those enzymes which
are so closely bound up with the protoplasm that they can be
isolated only after the cell has been destroyed. Their sphere of
activity is therefore limited to the inside of the cell. Such
endo -enzymes are present in every organ, and have also been
found in the egg,1 producing proteolysis and lipolysis. But since
such endo-enzymes are present in many, if not in all cells, no
special significance can be attached to their presence in the eggs.
The presence in the egg of secreted ferments analogous
to the ferments which can be obtained by simple extraction
from the digestive glands of the adult animal, would allow
of more definite conclusions. The presence of such ferments
1 Wohlgemuth, " fiber das Vorkornmen von Fermenten im Hiihnerei,"
Festschrift fur Salkowaki, 1904.
BIOCHEMISTRY OF THE SEXUAL ORGANS 277
has as yet not been proved with certainty, although the
diastatic action of egg yolk observed by Miiller and Masuyama l
points to the presence of a diastase analogous to the ptyalin
of the saliva.
Lower Vertebrates
The covering of the eggs of the lower Vertebrates is either of
the nature of a keratin, a scleroprotein rich in sulphur, similar to
the membrane of birds' eggs, or it is a mucoid substance. In
reptiles, like Calotes jubatus and Crocodilus biporcatus, and in
Elasmobranchs, like Raja and Scyllium, the membrane is stated
to consist of a keratin.2 In the membrane of the eggs of Tropi-
OO L
donotus,3 the British grass snake, a substance has been found
which is free from sulphur and resembles the elastin which
constitutes the elastic fibres of mammalian connective tissue.
A similar substance is stated to occur in the egg-membrane of
Mustelus Icevis* But these data are very scanty and hardly
convincing. In Amphibians like the frog the membrane has
been found to consist of pure mucin.5 In Teleostean fishes
it has been investigated in the case of the perch,6 and found
to be of the nature of a mucin.
It would be interesting to find out by systematic
investigations, such as those of Pregl 7 and Buchtala,8 whether
the chemical nature of the substances protecting the egg varies
with the different zoological classes, or whether it is dependent
upon external circumstances representing perhaps a case of
chemical adaptation.
1 Miiller and Masuyama, " liber ein diastatisches Ferment im Hiihnerei,"
Zeitschr. f. Biologic, vol. xxxix., 1900.
2 Krukenberg, Vergleichende Physiologische Studien : II. Reihe, 1 Abtei-
lung, 1882. Neumeister, " (Jber die Eischalenhaute von Echidna und der
Wirbeltiere im allgemeinen," Zeitschr. f. Biologic, vol. xiii., 1895.
3 Hilger, " Ueber die Chemischen Bestandteile des Keptilieneis " ; Berichte
der deutschen chem. Gesellschafl, vol. vi., 1873.
4 Krukenberg, loc. cit., 2 Abteilang, 1882.
5 Giacosa, " Etudes sur la Composition chimique de 1'CEuf et de ses En-
veloppes chez la Grenouille commune," Zeitschr. /. phys. Chemie, vol. vii., 1883.
6 Hammarsten, " Chemie des Fischeies," Skandinav. Arch. f. Physiologic,
vol. xvii., 1905.
7 Pregl, " Uber die Eihaute von Scyllium stellare und ihre Abbauprodukte,"
Zeitschr. f. phys. Chemie, vol. Ivi., 1908.
8 Buchtala, ibid.
278 THE PHYSIOLOGY OF REPRODUCTION
The investigations of Hammarsten brought to light the in-
teresting fact that a chemical change takes place in the cover
of the eggs during ripening. The immature eggs swell with
water, and a mucilaginous solution of mucus is formed, from
which the mucin may b? precipitated by the addition of acetic
acid. If mature eggs are treated with water they do not swell.
The water dissolves out the contents of the egg and the empty
covers of the eggs remain, and can be transformed into mucin
by weak alkali. During the ripening of the eggs there is there-
fore a change from mucin to mucinogen.
The composition of the eggs of fishes is essentially the same
as that of birds' eggs.
The organic constituents consist chiefly of protein, fats, and
phosphorised fats, with some cholesterin.
The following analysis of the ash of caviar l gives an idea
of the composition of the ash of the eggs of fishes :—
Total Ash . . K2O. Na20. CaO. Fe2O3. P2O6. Cl.
7'70 per cent. . 3'33 30'77 5*02 0'22 10*55 47'44
In the egg the protein is present in the form of a phospho-
protein. Valenciennes and Fremy, who were the first to isolate
this substance, called it Ichthulin. Later Walther showed that
this substance very closely resembles the vitellin present in
birds' eggs. On peptic digestion it yields an iron containing
pseudonuclein. A similar substance containing phosphorus and
iron was isolated from the eggs of the salmon by Noel Paton,
from cods"' eggs by Levene, and from perches' eggs by Ham-
marsten.2 The statement by Walther that ichthulin, on boiling
with mineral acids, splits off a reducing sugar and differs in this
respect from vitellin has not been confirmed by the later workers.
Ichthulin is probably identical with the crystalline material
observed in the eggs of the tortoise, the frog, the shark, and
other fishes, which is known morphologically under the name
of yolk-spherules or " Dotterplattchen." The unripe eggs of
the perch are embedded in a fluid from which a protein of the
nature of a globulin has been isolated. This protein received
1 Albu and Neuberg, Mineralstoffwechsel, p. 241.
2 Hammarsten, " Chemie des Fischeies," Skandinav. Arch. f. Physiologic,
vol. xvii., 1905. This paper contains a detailed review of previous work
done on this subject.
BIOCHEMISTRY OF THE SEXUAL ORGANS 279
the name " percaglobulin." l It is rich in sulphur, and is pre-
cipitated by weak hydrochloric acid. It has an astringent
taste, and possesses the remarkable property of forming pre-
cipitates with some glucoproteins such as ovomucoid, and with
polysaccharides such as glycogen and starch. This substance
could not be found when the eggs were mature, and does not
appear to be present in the ovaries of other fishes.
Very important and interesting results have been obtained
by systematic chemical examinations of the muscles and ovaries
of the salmon 2 and of the herring 3 at different seasons.
Extensive chemical changes take place in these animals during
the period of their reproductive activity. The reproductive
organs develop at the expense of the muscles, which diminish
in weight. This is best seen in the case of the salmon, since
this animal does not take any nourishment during its passage
up the rivers. In the case of the herring the conditions are not
quite so simple, because the herring feeds until spawning occurs,
although less food is taken in the later months.
In the case of the salmon, then, the ovaries are built up from
material contained in the muscle. The most marked change in
the muscle during that period is a loss of fat, with which the
muscles are loaded when the salmon leaves the sea. The protein
constituents of the muscle also diminish, but not to the same
extent as the fat. There is, further, a disappearance of the
inorganic phosphates of the muscle. From these substances
the ovaries build up their essential constituents — the phospho-
protein ichthulin and the phosphorised fats. The source of the
choline which is contained in the phosphorised fats is not yet
clear. This formation by the ovaries of phosphorised fats out
of fats and inorganic phosphates points to the important function
which these organic phosphorus compounds have to fulfil in
the developing organism (see above).
Not all the fat which disappears from the muscles reappears
1 Morner, " Percaglobulin ein charakteristischer Eiweisskorper aus dem
Ovarium des Barsches," Zeitschrift fur physiolog. Chemie, vol. xl.
2 Miescher, Histochemische und physiologische Arbeiten. Noel Paton and
others, "Report of Investigations on the Life-History of the Salmon in Fresh
Water," Report to the Fishery Board for Scotland, 1898.
3 Milroy, " Changes in the Chemical Composition of the Herring during
the Reproductive Period," Biochemical Journal, vol. iii, 1908, p. 366,
280 THE PHYSIOLOGY OF REPRODUCTION
in the ovaries as phosphorised fats. A portion of it serves as a
source of energy for the animal. The same applies to part of the
protein of the muscle.
The iron contained in organic combination in the ichthulin
of the ova is derived partly from the muscle and partly also
from the blood.
Together with the accumulation of fat in the muscles there
is a storing of a lipochrome, the characteristic pink pigment
of the flesh of the salmon. During its sojourn in the river this
pigment disappears in part from the muscles and is transferred
with the fat to the ova. This pink pigment is probably formed
from another yellow pigment, which is also present in the salmon,
and which is widely distributed in the animal kingdom, always
closely associated with fat. It is possible that the ingestion
and deposition of fat containing this yellow pigment are re-
sponsible for the formation of the pink pigment.
Invertebrates
The chemical composition of the eggs of Invertebrates does
not appear to be essentially different from that of the Vertebrate
eggs. The covering of the egg, which is often stated to be
chitin, has been investigated by Tichomiroff l in the egg of
Bombyx mori. He found it to be a protein body rich in sulphur,
and similar to the keratin substances of which the membrane
of the hen's egg is composed. The covering of the eggs of a
cephalopod — the cuttlefish — was investigated by von Fiirth.2
These eggs are united by their capsules, which are often
coloured black by pigment, and form what are popularly known
as " sea-grapes/' The covering or capsule is secreted by two
" nidamental glands/' which open into the oviduct, and it is
interesting to note that the substance secreted by these sexual
glands is a mucoid substance very similar to the pseudomucin
found in cysts of the human ovary (see Mammals, p. 264).
The protein substances in the eggs of Invertebrates have not
been closely investigated. Vitellin is said to occur.
1 Tichomiroff, " Chemische Studien iiber die Entwicklung der Insekten-
eier," Zeitschr. f. phys. Chemie, vol. ix., 1885.
2 Von Fiirth, " Uber Glycoproteide niederer Tiere," Hofmeister's Beitrage,
vol. i., 1901.
BIOCHEMISTRY OF THE SEXUAL ORGANS 281
The eggs of insects are comparatively rich in phosphorised
fats. By extraction with alcohol and ether, Dubois * isolated
from locusts' eggs a yellowish oil containing 1*92 per cent,
phosphorus.
Glycogen, purine bases, and cholesterin have been found in
the eggs of Bombyx. The changes which take place during
incubation, in the chemical composition of these eggs, have been
investigated by TichomirofL2
The following table shows that a considerable amount of
purine bases are formed during incubation. At the same time
the fat and glycogen diminish in amount, while the cholesterin
remains practically unchanged and the phosphorised fats in-
crease slightly in amount.
,
Before
After
Incubation.
Incubation.
Per Cent.
Per Cent.
Purine bases .
0'02
0-2
Glvcogen
.
1-98
0-74
Present in rFat
8-08
437
Ethereal J Phosphorised fat .
Extract [Cholesterin .
1-04
0-40
1-74
0-35
On the whole the changes are similar to those observed
in hens' eggs, except that glycogen is present in considerable
quantities in the egg and disappears during development as well
as the fat, while the phosphorised fats are apparently not utilised
as a source of chemical energy. The " energy of development "
is very considerable, and,, calculated as a percentage of the
chemical energy contained in the whole egg, is as great as in the
case of the developing hen's egg.3
The pigments have been studied especially in the eggs of
Crustacea. From the eggs of Maja squinado, Maly 4 isolated
1 Dubois, " Sur 1'huile d'CEufs d' la Sauterelle d'Algerie (Acridium
pzlerinum)," Gomptes Rendus, vol. cxvi., 1893.
2 Tichomiroff, loc. cit.
:{ Farkas, " Uber den Energieumsatz des Seidenspinners wahreud der
Entwicklung im Ei u. wahrend der Metamorphose," Pjluger's Archiv,
vol. xcviii., 1903. See Appendix to this Chapter, p. 302.
4 Maly, " tiber die Dotterpigmente," Berichte der Akademie der Wissen-
schaften, in Wien, vol. Ixxxiii., 1881.
282 THE PHYSIOLOGY OF REPRODUCTION
two pigments — a red pigment, Vitellorubin, which is extremely
sensitive to light, and a yellow pigment, Vitellolutein. These
pigments belong to the lipochromes, which have been men-
tioned above. Krukenberg 1 has examined the pigments of a
number of other Invertebrates. All these lipochromes have
characteristic absorption spectra.
The lipochromes of Maja are of special interest, because a
similar pigment, Tetronerythrin, has been found in the blood
of Maja and other Crustacea. The amount present in the blood
shows considerable variation. According to Heim 2 it is com-
pletely absent in the blood of the male, and appears in the blood
of the female during ovulation. At this period also the ovaries,
which usually have a yellowish or whitish colour, become first
bright yellow and then red. In Heim's 3 view this lipochrome
is not formed in the ovary but in some other organ of the body,
and passes at the period of ovulation into the blood, which
carries it to the ovaries.
The same author, together with Abelous,4 has proved the
existence of some ferments in watery and glycerine extracts of
the eggs of various Crustacea. A diastatic, a tryptic, and an
inverting ferment were found. They are stated to increase in
strength during the maturation of the ovum.
THE MALE GENERATIVE ORGANS
The Semen
The semen, i.e. the fluid discharged by an ejaculation, is
the secretory product of the testis, epididymis, vesiculse
seminales, prostate and Littre's glands. In Man it is a thick,
viscous, yellowish, opalescent fluid, which after ejaculation
solidifies at first and afterwards becomes fluid again. It has a
peculiar smell, which becomes even more noticeable on heating.
1 Krukenberg, Vergleichende physiologische Studien : II. Reihe, 3
Abteilung, 1882, p. 6.
2 Heim, "Sur les Pigments des (Eufsdes Crustacds," Comptes RendusSoc.
Biol., vol. xliy., 1892, p. 467.
3 Heim, Etudes sur le Sang des Crustacea, Paris, 1892.
4 Abelous and Heim, " Sur les Ferments des (Eufs des Crustaces," Compt.
Rend. Soc. Biol., vol. xliii., 1891, p. 273.
BIOCHEMISTRY OF THE SEXUAL ORGANS 283
Its reaction is alkaline. Its specific gravity lies between 1*02
and r04. The amount discharged in an ejaculation is given
differently by different authors, and probably varies with
different individuals, and even with the same individual _at_
different times. From the figures given in the literature
5 grammes may be taken to be the average amount.1
According to Slowtzoff,2 human semen consists roughly of
90 per cent, water and 10 per cent, solids, which, on incineration,
yield about 1 per cent, of ash. The solids contain 2 '3 per cent,
of proteins, of which a nucleoprotein, traces of albumen and
mucin, and an albumose-like substance have been identified.
The quantitative relation of the various solids in 100 parts
of fresh semen can be seen in the following table : — •
Average Values.
Per Cent.
Water 90'32
Dry residue 9'68
Inorganic salts 0'90
Organic material ...... 8*78
Ether soluble matter 0'17
Extractives soluble in alcohol and water . . 6'11
Protein substances 2-09
In the ash K, Na, Ca, Mg, P, Fe, and S have been found.
The quantitative analysis of the ash reveals a remarkably
large amount of calcium and phosphoric acid — about 20 ]3er cent.
Ca and 30 per cent. P205. The amount of calcium excreted in
one ejaculation is, therefore, about 0*01 grm., and exceeds that
contained in an equal quantity of lime-water. Analyses of the
semen of other Mammals do not appear to have been made, but
it is unlikely that there are any essential differences. Since during
the breeding season about fifty sheep are served by one ram, it
is evident that a profound change must take place in the meta-
bolism of phosphorus and calcium during that period. Is it
1 Acton, Functions and Disorders of the Reproductive Organs, 3rd
Edition, London, 1862. Lode, " Untersuchungen tiber die Zahlen und
Regenerations Verhaltnisse der Spermatozoiden bei Hund und Mensch,"
Pfliiger's Archiv, vol. 1., 1891. Mantegazza, Gaz. Med. Ital., Lombardia,
1866, quoted from Lode.
2 Slowtzoff, "Zur Chemie des menschlichen Sperma," Zeitschrift f. phys.
Chemie, vol. xxxv., 1902.
284 THE PHYSIOLOGY OF REPRODUCTION
not possible that the effects which are usually ascribed to a
hypothetical " internal secretion " of the testis are partly due
to such a direct connection with the metabolism of the body ?
The nature of the influence which the sexual glands exert
upon the metabolism of the body is very complex, and has not
yet been fully cleared up. Various observers have obtained
very contradictory results. Since this subject will be dealt
with in another chapter, we will refer to it here only in so far
as it has any bearing on the calcium and phosphorus metabolism.
On this point there is conclusive evidence of a morphological
nature both for the male and for the female organism. Castra-
tion leads to a marked increase in the growth of the long bones.
This fact, which is due to a retardation of the process of endo-
chondral ossification taking place in these bones, accounts for the
increase in stature of eunuchs and of castrated animals (see p. 306).
Similar evidence, although of a more complex character, is
afforded in the case of the female by the relationship which
undoubtedly exists between the ovaries and osteomalacia, a
disease consisting mainly in a decalcification of the bones. It
is produced probably by an abnormal function of the ovaries,
since removal of the ovaries markedly improves, and sometimes
cures, this condition (see p. 353). In pregnancy and parturition
there is what one might call a " physiological osteomalacia " of
the pelvic bones ; and the activity of the mammary gland during
lactation must necessarily bring about an increased calcium meta-
bolism, since milk contains a very large amount of this element.
The organic substances in the semen may be divided into
two groups. If the semen is examined microscopically it is
found that it contains, on the one hand, cellular elements — viz.
the spermatozoa and lymphocytes, partly in a state of de-
generation ; on the other hand, organic material which is partly
amorphous and partly crystalline.
The amorphous material consists of :—
1. Fine albuminous granules intermixed with a few fat
globules and pigmented granules.
2. Small globules of about half the size of a red blood-
corpuscle consisting of a lipoid substance.
3. Oval amyloid bodies composed of concentric layers.
These are, however, not invariably found.
BIOCHEMISTRY OF THE SEXUAL ORGANS 285
4. The so-called " sympexions " of Robin, oval concrements
of a wax-like substance, the nature of which is not known.1
The crystalline substances appear only when the semen is
inspissated. They present various forms — prisms, rosettes, &c.,
— and are sometimes called " Bottcher's spermine crystals."
They are insoluble in alcohol, ether, and chloroform, soluble in
hot water, in formol, dilute alkalies and alkali carbonates, and
in dilute acids. They are coloured black by a solution of
iodine in potassium iodide (Florence's reagent). Like many
ammonium-bases spermine gives a characteristic colour reac-
tion with alloxan.2 On evaporating a solution of spermine to
which a saturated solution of alloxan has been added, a red
colour appears, which changes into violet on the addition
of alkali. The spermine crystals are not identical, as was
formerly believed, with the crystals found in the blood of
leucsemic patients (" Zenker's crystals "), or with the " Charcot-
Leyden crystals " which occur in the sputum of asthmatic
persons.
Their chemical nature is still a matter of doubt. According
to Schreiner, they are the phosphate of an organic base spermine,
C2H5N, which Ladenburg and Abel 3 believed to be Aethylenimin
C2H4NH. This is disputed, however, by Majert and Schmidt,
who ascribe to the base the formula C5H14N2, and by Poehl,4
who has attributed very remarkable properties to this substance.
According to Poehl, spermine is possessed of marked pharma-
cological properties, and has a powerful influence on the meta-
bolism. It is recommended by Poehl as a valuable therapeutic
agent. His statements have not been confirmed by other ob-
servers— for example Dixon 5 — and his views are now not
generally accepted.
1 Cohen, " Die krystalliniscben Bildungen des mannlichen Genitaltraktus,"
Centralhlatt f. allg. Pathologie u. pathol. Anatomie, vol. x., 1899. (This paper
gives a very complete bibliography.)
2 Poehl, "Weitere Mitteilungen liber Spermin," Berliner klin. Wochen-
schrift, 1891.
3 Ladenburg and Abel, " Uber das Aethylenimin," Ber. der deutschen
chem. GeseUschaft,vol.xxi., 1888.
4 Poehl, Die Physiologisch-Chemischen Qrundlagen der Spermintherapie,
Petersburg, 1898.
5 Dixon, " The Composition and Action of Orchitic Extracts," Journal of
Physiology, vol. xxvi., 1901.
286 THE PHYSIOLOGY OF REPRODUCTION
Choline, which gives the same reactions as spermine with
iodine and alloxan, has also been stated to occur in the
semen.
The various glands of the genital tract contribute to the
formation of the semen in the following way :—
The spermatozoa are formed in the testis, which secretes an
albuminous fluid as the medium in which the spermatozoa
move about. Crystals smaller than the crystals of spermine-
phosphate have been observed by Lubarsch l in the tubules of
the testis. They are insoluble in formol and 50 per cent,
acetic acid, and swell up under the action of alkali. Other
crystalloid rod-like formations in the interstitial cells have been
described by Reinke 2 and von Bardeleben.3 The nature of
these crystals, which have been found so far only in human
testes, is unknown. Amyloid bodies, which are coloured blue
with difficulty by iodine, have been observed by Dares te.
The secretion of the epididymis has not been chemically
investigated. The vesicula) seminales secrete a substance of a
protein nature. Both these secretions have a faintly alkaline
reaction.
In the guinea-pig the protein substance secreted by the
vesiculae seminales clots if brought in contact with blood. This
property is perhaps a means whereby fertilisation is ensured,
since in the guinea-pig coitus may take place immediately
after the termination of the previous pregnancy, when the
uterus is still widely dilated. This unfavourable condition is
compensated for by the formation of a clot brought about by
the action of the semen on the blood which is still present in
the uterus.4
The prostate gland secretes an opaque fluid having a faintly
acid reaction (which may become neutral or alkaline in in-
1 Lubarsch, " tiber das Vorkommen Krystallinischer und Krystalloider
Bildungen in den Zellen des Menschlichen Hodens," Virchow's Archiv,
vol. cxlv., 1896.
2 Reinke, " Beitrage zur Histologie des Menschen," Archiv f. mikroskop.
Anatomic, vol. xlvii., 1896.
3 Bardeleben, " Beitrage zur Histologie des Hodens und zur Sperrnato-
genese beim Menschen," Archiv f. Anatomie u. Physiologic, Anatomische
Abteilung, Supplement, 1897.
4 Landwehr, "fiber den Eiweisskorper der vesicula seminalis der Meer-
schweinchen," Pfluger's Archiv, vol. xxiii., 1880.
BIOCHEMISTRY OF THE SEXUAL ORGANS 287
flammatory conditions of the prostate). It contains spermine,1
which, when brought together with the phosphates secreted
by other genital glands, forms the characteristic " Bottcher's
crystals/'
The secretion of the prostate also contains the substancT
which gives the characteristic smell to the ejaculated semen,
the lecithin-like globules, and a protein substance. The state-
ment that this protein is an albumose is probably not correct,
since albumoses have never been found to occur in a living cell.
Camus and Gley 2 found in the prostatic secretion of some
animals a ferment, vesiculase, which has the property of
coagulating the fluid in the vesiculse seminales. The presence
of this ferment in the ejaculated semen produces the formation
of a coagulum. This ferment appears to have the function
of ensuring fertilisation, since it occurs only in those species
where the contact between male and female is of very short
duration. (See p. 233.)
Cowper's glands secrete a stringy mucinous substance.
If a solution of iodine in potassium iodide is added to semen,
brown crystals are formed (Florence's reaction). This reaction
is common to many substances belonging to the group of organic
ammonium bases. One of the best-known members of this
group is choline, which forms part of the lecithin molecule, and
is, therefore, a constituent of almost every animal cell. Pro-
bably the reaction is not due to spermine, as Florence 3 states, but
to choline, as Bocarius4 believes, since other secretions and
tissue extracts which do not contain spermine give the same
reaction.
Another reaction for semen, which is much more specific,
has been discovered by Barberio. By the addition of picric
acid, fine rhombic or needle-shaped crystals are formed. It is
doubtful which substance is responsible for this reaction. The
1 Fiirbringer, " Die Storungen der Geschlechtsfunktion des Menschen " ;
in Nothnagel, Pathologic u. Therapie., vol. xix., Part III., 1895.
2 Camus and Gley, "Action Coagulante du Liquide Prostatique sur le
Contenu des Vesicules Sdminales," Comptes Rtndus, vol. cxxiii., 1896.
3 Florence, " Du Sperme et des Taches du Sperme," Archives d'Anthro-
pologie Criminate, vol. xi., 1896 ; vol. xii., 1897.
4 Bocarius, " Zur Kenntniss der Substanz welche die Bildung von Florence-
chen Krystallen bedingt," Zeitachrift f. phyaiologische Chemie,vo\. xxxiv., 1902.
288 THE PHYSIOLOGY OF REPRODUCTION
observations of Little John and Pirie l show that the substance
which forms the crystalline picrate is secreted by the prostate
and by Cowper's glands, and, further, that this substance appears
to be specific for human semen, since a negative result is ob-
tained with the semen of monkeys, rabbits, and rats.
THE CHEMISTRY OF THE SPERMATOZOON 2
Owing to the brilliant work of Miescher,3 which has been
continued by Kossel 4 and his pupils, our knowledge of the
chemistry of the spermatozoon is more complete than that of
any other cell.
Thanks to the intelligent generosity of the head of a large
fishery concern in Bale, Miescher obtained a liberal supply of
the milt of the salmon, the sexual organs of which develop
during the passage up the Rhine. By controlling his mechanical
manipulations by means of histological observations Miescher
was able to investigate separately the different morphological
elements of the spermatozoa. The tails of the spermatozoa are
very rich in phosphorised fats, and contain besides a typical
protein, cholesterin, and fat, in the following proportions :—
Proteins . . . . ". 41-90 per cent.
Phosphorised fats . . . 31-83 „
Cholesterin, fats . . . 26-27 „
Similar conditions were found to exist in the case of other
fishes and in the case of the ox. The heads were found to
contain only traces of fat, lecithin and cholesterin, and to be
composed almost entirely of a substance very rich in phosphorus.
This on further investigation proved to be a combination of
a basic substance, very rich in nitrogen, which Miescher called
1 Littlejohn and Pirie, " The Micro -Chemical Tests for Semen," Edin.
Med. Jour., 1908. (This paper contains references to the literature.)
2 For a detailed account of this subject and the literature see Burrian,
" Chemie der Spermatozoen, I.," in Ergebnisse der Physiologic, vol. iii., 1804,
and "Chemie der Spermatozoen, II.," in Ergebnisse der Physiologic, vol. v.,
1906.
3 Miescher, Histochemische und Physiologische Arbeiten. Gesammelt und
Herausgegeben von Seinen Freunden, vol. ii., Leipzig, 1897.
4 Kossel, " tiber die einfachsten Eiweisskorper," Biochemisches Centralblatt ,
vol. v., 1906-7, Part I.
BIOCHEMISTRY OF THE SEXUAL ORGANS 289
protamine, and a substance rich in phosphorus, having the
nature of an acid and belonging to the group of substances
known as nucleinic acids, which occur in the nuclei of somatic
cells in combination with protein substances as the so-callecL
nucleoproteins.
The comparative chemical investigations of Kossel showed,
that while the nucleinic acid radicle present in the spermatozoa
of various species of fishes shows only very little variation,
the basic part is different for each species. It has, therefore,
been found convenient to distinguish these basic substances
by separate names, derived from the Latin names of the species
of the fish in which they occur. The basic substance of the
head of the spermatozoon of the salmon is salmine, that of the
herring clupeine, and so on. Since they have certain general
chemical and physical characters in common they have been
classed together in a group, which has received the name " Pro-
tamine/' which was originally used by Miescher to denote the
basic substance in the spermatozoa of the salmon.
The protamines are strongly basic substances which absorb
carbonic acid from the air. They are soluble in water, insoluble
in alcohol and ether ; not coagulable by heat ; free from sulphur.
They are very rich in nitrogen, the percentage amount varying
from 33 per cent, to 25 per cent., while that of an albumen or
globulin is about 16 per cent. They give a strong biuret re-
action. Like other proteins, they are precipitated by tannic
acid, phosphotungstic acid, picric acid, and ferrocyanic acid ;
but while the proteins are precipitated by these reagents in acid
solution only, the protamines, by virtue of their basic character,
form a precipitate with these reagents even in alkaline solution.
They form compounds with the salts of the heavy metals (copper,
mercury, silver, platinum). The protamines combine with many
other protein substances in neutral or faintly alkaline solution,
so that a precipitate is formed if, for example, a solution
of protamine is added to a solution of caseinogen.1
If injected into an animal they have a strongly toxic action,
even if small doses are given.2
1 Hunter (A.), " (Jber die Verbindungen der Protamine mit anderen
Eiweiss-korpern," Zeitschrift f. phys. Chemie, vol. liii. 1907.
2 Thompson, " Die physiologische Wirkung der Protamine," Zeitschrift f.
physiol. Chemie, vol. xxix., 1899.
T
290 THE PHYSIOLOGY OF REPRODUCTION
Although differing in many respects from the protein sub-
stances, the protamines have been shown by Kossel to have a
constitution so similar to that of the proteins that they are now
considered to represent one group of the protein substances.
The study of the products of hydrolytic decomposition shows
that while in the case of the typical proteins, such as the proteins
of muscle, of milk, or of the serum, the nitrogen is bound up in
the form of a great many different substances, e.g. tyrosine,
leucine, alanine, glycine, cystine, &c., of which as many as fifteen
have been isolated, the protamine molecule is composed of only
a few constituent substances. And, further, while in the case of
the typical proteins the main bulk of the substance obtained on
hydrolysis belongs to the monoamino acids, the protamines are
composed largely of the diamino acids : arginine, lysine, and
histidine, which, from their basic nature and the fact that they
contain six carbon atoms, have received the name " hexone-
bases."
Of these the most important one is arginine, which, on
boiling with baryta, is decomposed into urea and diamino-
valerianic acid (ornithin), and has the structure —
NH2 NH2
NH = C-NH-CH2-CH2-CH2-CH-COOH
In salmine, for instance, eight-ninths of the nitrogen is bound
up as arginine, while the remainder of the nitrogen is present
in the form of monoamino acids, viz., serine, monoamino valerianic
acid and proline, in the following proportions : 10 molecules of
arginine + 2 molecules of serine + 2 molecules of proline + 1
molecule of aminovalerianic acid. Similar relations are found
to exist in the case of scombrine and clupeine. In both these
protamines eight-ninths of the total nitrogen is present in the
form of arginine, which is combined with alanine and proline
in the case of scombrine, and with alanine, proline, serine, and
aminovalerianic acid in the case of clupeine.
Since eight-ninths of the nitrogen of these three protamines
is present in the form of arginine, and since arginine contains
four nitrogen atoms, while the amino acids with which it is
combined contain only one nitrogen atom, it follows that in
BIOCHEMISTRY OF THE SEXUAL ORGANS 291
these three protamines the number of arginine molecules must
be twice as great as the total number of monoamino acid
molecules present in the protamine molecule.
The investigations of Kossel and Pringle l have shown tha_t
substances can be obtained by partial hydrolysis of these
protamines, the so-called " protones," which represent inter-
mediate decomposition products between these protamines
and the amino acid units of which the protamines are built up,
and that these protones again contain eight-ninths of their total
nitrogen in the form of arginine. It follows, then, that the
molecules of salmine, scombrine, and clupeine have a symmetrical
structure, and are built up of molecular complexes containing
always twice as many arginine molecules as monoamino acid
molecules.
In other protamines the amount of arginine is smaller,
while lysine is found to be present. At the same time the
number of monoamino acids bound up in the protamine
molecule increases so that the different protamines exhibit
varying degrees of complexity. Ammonia and certain mono-
amino acids (glycocoll, phenylalanine, glutaminic acid, aspartic
acid, the sulphur -containing cystine) are never present.
In the case of some fishes — e.g. Gadus morrhua? Lota vulgaris 3
—the basic substances isolated from the spermatozoa differ
essentially from the protamines, and in character more resemble
the typical proteins. Their nitrogen content varies between
16 per cent, and 18 per cent. On hydrolysis the yield of
diamino acids is very much smaller than in the case of the
protamines. Only 30 to 40 per cent, of diamino acids, among
which arginine again preponderates, are obtained. Accordingly
they are not so strongly basic as the protamines. They contain
cystine. They are precipitated by ammonia, a reaction which
the protamines do not give. They resemble in their be-
haviour substances which have been isolated from the nuclei
of somatic cells, e.g. the blood corpuscles of the fowl, the
1 Kossel and Pringle, " Uber Protamine und Histone," Zeitschrift f. phys.
Chemie, vol. xlix., 1906.
2 Kossel and Kutscher, " Beitrage zur Kenntniss der Eiweisskorper,"
Zeitschr.f. phys. Chemie, vol. xxxi., 1900.
3 Ehrstrom, " Uber ein neues Histon aus Fischsperma." Zeitschrift f.
phys. Chemie, vol. xxxii., 1901.
292 THE PHYSIOLOGY OF REPRODUCTION
thymus, &c., and which form another class of the protein sub-
stances, to which the name histone has been given. In their
properties and their composition these substances, therefore,
take a place between the typical proteins and the protamines.
The substance isolated from the spermatozoa of the carp,
cyprinine (or rather the two cyprinines, since two slightly
different substances have been isolated), is on the border-line
between the protamines and the histones. The cyprinines do
not contain any cystine, they are not precipitated by ammonia,
and only about 35 per cent, of their total nitrogen is present
in the form of diamino acids, mainly as lysine in the one of the
two cyprinines.1
The chemical differences which exist between the spermatozoa
of the different species and orders do not show any connection
with the zoological relationship.
The significance of the presence of histones in the spermatozoa
of some fishes becomes more apparent if the development of the
sexual organs is considered.
It was Miescher who pointed out that in the salmon the
sexual organs develop at the expense of the muscular system
and that the salmine deposited in the testis during the breeding
season must be derived from the proteins of the muscle, since
the fish does not take any food during that period. A com-
parison between the amount of arginine present in salmine,
and that present in the muscle of the salmon shows 2 that all
the arginine deposited as salmine during the breeding season
can be accounted for by the arginine which becomes available
by the involution of the muscular elements.
This result would suggest that the formation of salmine is
not due to a profound chemical alteration of the various con-
stituents of the muscle-proteins, transforming the divers sub-
stances into arginine, but rather to a gradual enrichment in
arginine of the muscle protein by the splitting off of a number
of the other constituent substances.
1 Kossel and Dakin, " Beitrag zum System der einfachsten Eiweisskorper,"
Zeitschrift f. phys. Chemie, vol. xl., 1904.
2 Kossel, " Einige Bemerkungen Uber die Bildung der Protamine im
Thierkorper," Zeitschrift fur physiologische Chemie, vol. xliv., 1905. Weiss,
" Untersuchungen iiber die Bildung des Lachs-Protamins," Zeitschrift fur
physiologische Chemie, vol. lii., 1907.
BIOCHEMISTRY OF THE SEXUAL ORGANS 293
The investigation of the unripe spermatozoa of the salmon l
and of the mackerel 2 has shown indeed that instead of a pro-
tamine a histone is present, i.e. a substance which represents
the transition stage between the typical proteins and the
protamines.
It would appear, therefore, that in the fishes the chemical
processes which lead to the formation of the spermatozoa consist
of a rearrangement of the constituents of the proteins of somatic
tissue, so that a gradual accumulation of the basic substances
rich in nitrogen takes place. This change leads at first to the
formation of histones, and in some species stops here. In the
majority of cases the change proceeds to the formation of sub-
stances belonging to the protamines.
In the case of some Invertebrates (Arbacia pustulosa,3
Sphcerechinus granularis 4) the spermatozoa have been in-
vestigated and histones have been found to be present.
Of the higher Vertebrates, the spermatozoa of the frog,
the cock, the boar, and the bull have been examined,5 but
neither protamines nor histones were found.
The acid substance isolated from the spermatozoa, the
nucleic acid, does not show any great variation in the different
species and classes of animals. It is, in fact, very similar to
the nucleic acid present in the nuclei of somatic cells, and is
probably identical with the nucleic acid prepared from the
thymus. These nucleic acids do not belong to the proteins,
but they exist in the cell always in combination with proteins
as nucleins or as nucleoproteins, according to the amount of
protein present in the combination.
The nucleic acids are dry, pulverulent, white substances
of a decidedly acid character, containing 9 to 10 per cent, of
1 Miescher, " Physiologisch-Chemische Untersuchungen iiber die Lachs-
milch," Histochemische Arbeiten, Archiv f. Experimentelle Pathologic u.
Pharmakologie, vol. xxxvii., 1896-1897.
2 Bang (I.), "Studien iiber Histon," Zeitschrift f. physiolog. Chemie,
vol. xxvii., 1899.
3 Mathews, " Zur Chemie der Spermatozoen," Zeitschrift f. phys. Chemie,
vol. xxiii.,1897.
4 Kossel, " Uber die einfachsten Eiweisskorper," Biochemisches Cen-
Iralblatt, vol. v., 1906-7.
5 Miescher, loc. cit., "Die Spermatozoen einiger Wirbelthiere," Histo-
chemische Arbeiten ; Mathews, loc. cit.
294 THE PHYSIOLOGY OF REPRODUCTION
phosphorus, not easily soluble in cold water, but readily dis-
solved by alkalies or ammonia. They are precipitated from
their solutions by mineral acids and by alcohol. They form
insoluble salts with the heavy metals and with barium,
calcium, and strontium. If pure, they do not give the colour
reactions for proteins. They rotate polarised light to the
right. A solution of nucleic acid, acidified with acetic acid,
gives a precipitate with protein solutions. By boiling the
watery solutions the nucleic acids are partially decomposed.1
Complete hydrolysis is brought about by treatment with hot
acids. The main products of hydrolysis which are thus
obtained can be grouped under five headings :—
1. Phosphoric acid.
2. La3vulinic acid, a substance formed by the oxidation
of carbohydrates, and indicating the presence of a hexose (some
nucleic acids contain a pentose).
3. Derivatives of purine —
(1) N = CH(6)
(2) HC C (5)-NH(7)\
I! II >CH (8)
(3) N-C (4)-N (9)^
namely —
Adenine = 6 - Aminopurine ; Hypoxanthine = 6 - Oxypurine ;
Guanine = 2 Amino — 6 Oxypurine ; Xanthine = 2 — 6 Dioxypurine.
Of these only adenine and guanine are present as such in
the nucleic acid molecule, while hypoxan thine and xan thine
are formed from them in the process of hydrolysis by a
secondary reaction.
4. Derivatives of pyrimidine —
(1) N = CH(6)
(2) HC CH (5)
II II
(3) N - CH (4)
namely—
Cytosine = 6 Amino — 2 Oxypyrimidine
Uracil = 2 - 6 - Dioxypyrimidine
Thymine = 5 Methyl-2-6 Dioxypyrimidine (Methyl-Uracil).
1 For literature for nucleic acid see Steudel, " Nucleine, Nucleinsauren
und ihre Spaltungsprodukte," Biochemisches Centralblatt, vol. vi.,1907; also
Burrian, loc. cit. ; Levene, Zeitschr.f. phys. Chemie, vols. xxxii. to 1., Biochem.
Zeitschr., vols. iv., v., and ix.
BIOCHEMISTRY OF THE SEXUAL ORGANS 295
Of these cytosine and thymine are present as such in the
nucleic acid molecule, while uracil is formed from cytosine by
a secondary reaction in the process of the splitting up of the
nucleic acid.
Reference has already been made to the fact that in the
salmon the material for the growth of the testis is supplied
by the muscle undergoing atrophy. The analogy existing
between the glycophosphoric acid which forms the " skeleton "
of the nucleic acid, and the glycerophosphoric acid which
forms the skeleton of phosphorised fats, suggests that the
glycerophosphoric acid present in the muscle as phosphorised
fat furnishes the material from which the glycophosphoric acid
bound up in the testis as the nucleic acid is formed. This
view is supported by the fact 1 that, during the period of the
growth of the testis, the blood of the salmon is exceptionally
rich in phosphorised fats, and that the tail of the spermatozoon
is also very rich in phosphorised fats. It would appear that
these substances, after having been transported to the testis, are
there built up partly into the nucleus of the spermatozoon,
while part remains accumulated in the tail of the spermatozoon
as reserve material.
The origin of the purine and pyrimidine derivatives which
form part of the nucleic acid molecule is as yet obscure. In
the case of the developing ovum it has been shown (see p. 269)
that the living cell has the power of synthesising these sub-
stances. But the substances which supply the material for their
formation, and the reactions which lead to it, have not yet been
revealed.
The substances detailed above represent all the constituent
parts of the nucleic acid molecule, so that it is possible to recon-
stitute the nucleic acid from the products of its decomposition.
According to Steudel,2 the process of hydrolysis may be expressed
by the following equation : —
C43H57N15030P4 + 4H20 = C,H6N50 + C5H5N5 + C6H6N2O2 + C4H5N30
Nucleic acid. Guanine. Adenine. Thymine. Cytosine.
+ C24H44030P4.
1 Miescher, loc. cit.
2 Steudel, " Die Zusammensetzung der Nukleinsauren aus Thymus u. aus
Heringsperma," Zeitschr. f. phys. Chemie, vol. liii., 1907.
296 THE PHYSIOLOGY OF REPRODUCTION
The non-nitrogenous part is split up further according to the
following equation : —
C24HM030P4 + 4H20 + 20 = 4C6H1206 + 4HPO3.
Hexose Metaphosphoric
sugar. acid.
In other words, the " skeleton " of the nucleic acid molecule
is formed by four molecules of metaphosphoric acid combined
with four molecules of a sugar : * a tetraglyco-metaphosphoric
acid, similar to the glycerophosphoric acid which forms the
" skeleton " of phosphorised fats. In the nucleic acid molecule
this glycophosphoric acid is combined with four different nitro-
genous substances, of which two are pyrimidine derivatives and
two are purine derivatives.2
It is an interesting fact that while nucleic acid prepared
from ripe spermatozoa does not contain pentoses, these sub-
stances are stated to be present in the nucleic acid of the testis
of the bull,3 which represents the acid constituent of the nuclei
of the sexual element in the various stages of their development.
Since the statement of the presence of a pentose in the nucleic
acid from the testis of the bull is based only on the preparation
of an osazone, further investigation on this point and analytical
data are necessary before it can be accepted.
The observations of Miescher 4 allowed of a quantitative esti-
mation of the amount of nucleic acid and protamine present in
the head of the spermatozoa of the salmon after the fat had
been removed. 6O5 per cent, of nucleic acid was found to be
combined with 35 '5 per cent, of salmine, so that 96 per cent, of
the head of the spermatozoon consists of protamine nucleate.
This protamine nucleate is, however, not of the same nature
in different parts of the head, the outer layer containing a basic
nucleate rich in protamine, while the inner portion is composed
of an acid nucleate poorer in protamine.
1 The sodium-salt of a tetraphosphoric acid can be prepared by fusing
together the sodium metaphosphate and pyrophosphate (Kraut and Uelsmann,
Liebig's Annalen, vol. cxviii., 1861). The organic derivatives of this base
have not yet been studied.
2 For a slightly different view of the constitution of nucleic acid, see
Burr'ian in Ergebnisse dcr Physiologic, vol. v., loc. cit.
3 Steudel, " Tiber die Kohlenhydratgruppe in der Nukleinsanre," Zeit-
schrift f. physiolog. Chemie, vol. Ivi., 1908.
4 Miescher, Histochemische Arbeiten.
BIOCHEMISTRY OF THE SEXUAL ORGANS 297
The same quantitative relations have been shown to exist
in the spermatozoa of the herring,1 and similar conditions may
be assumed to exist in the case of the spermatozoa of other
animals, the only difference being the nature of the protein
molecule which is combined with the nucleic acid. It is a
protamine or a histone in the case of the fishes, but a typical
protein in the case of the higher Vertebrates.2
Of the remaining 4 per cent, about one half consists of in-
organic salts, mainly calcium phosphate and calcium carbonate,
while the other half consists of an organic substance, the com-
position of which has not yet been recognised. The most
important fact known about it is that it contains 0'12 per
cent, iron in organic combination. The presence of iron can
be recognised only after incineration. To this iron-containing
organic substance Burrian 3 applies the name " Karyogen," a
word originally coined by Miescher to designate the residue which
he obtained after what Schmiedeberg's 4 calculations showed to
be an incomplete extraction of the protamine and nucleic acid
from the heads of the spermatozoa of the salmon. Since Macallum 5
was able to demonstrate by means of a microchemical method
the presence of iron in the chromatin of the nuclei of cells, it
seems possible that the " Karyogen " represents the chromatin
substance of the spermatozoon.
The chemical analysis of the spermatozoon is therefore
complete. It shows that the tail is very rich in phosphorised
fats which are accompanied by cholesterin, fats, and a typical
protein. The head consists almost entirely (96 per cent.) of
a substance — a nucleoprotein — one component of which is
constant for the different species and classes — the nucleic
1 Bendix and Elstein, " liber den Pentosengehalt tierischer und mensch-
licher Organe," Zeitschriftf. allgem. Physiologic, vol. ii., 1902.
2 Mathews, " Zur Chemie der Spermatozoen," Zeitschrift /. phys. Ckemie,
vol. xxiii., 1897.
3 Burrian, Ergebnisse der Physiologif, vol. v., 1906.
4 Miescher, " Physiologisch-chemische Untersuchungen iiber die Lachs-
milch, nach den hinterlassenen Aufzeichnungen u. Versuchsprotokollen des
Autors bearbeitet u. herausgegeben von O. Schmiedeberg," Arch. f. Experi-
mentelle Pathologic u. Pharmakologie, vol. xxxvii., 1896, and in Histochemische
u. Physiologische Arbeiten von Miescher.
5 Macallum, " On the Demonstration of the Presence of Iron in Chromatin
by Microchemical Methods," Proc. Roy. Soc., vol. 1., 1892.
298 THE PHYSIOLOGY OF REPRODUCTION
acid. The other more or less basic component varies widely
for the different classes of Vertebrates, and shows minor
variations for the different species in any one class. Besides
this nucleoprotein, another organic substance, containing iron in
organic combination, is present in very small amounts.
It is perhaps natural that attempts should have been made
to associate these different substances with the functions of the
spermatozoon. But such speculations are hardly justifiable
until our knowledge of the nucleus of the ovum is as complete
as it is in the case of the male nucleus. At present we know
practically nothing of the chemical composition of the nucleus
of the ovum. Nor is it likely — and Miescher himself clearly
recognised this — that the intricate processes which are con-
nected with fertilisation and heredity are directly dependent
upon such crude chemical facts as the percentage of arginine
or serine, or the composition of nucleic acid.
We are on safer ground when we consider the head of
the spermatozoon simply as a typical nucleus, and when we
draw deductions from the chemical composition of the nuclear
material of the spermatozoon, as to the functions of the nucleus
generally.
It is a very suggestive fact that the nucleus — that is to say,
that part of the cell which is pre-eminently concerned in the
new formation of living material — is distinguished by the presence
of pyrimidine and purine derivatives, substances rich in nitrogen,
which are arranged in a chain of alternating C and N atoms.1
In the spermatozoon, where the nuclear function finds its
most pronounced expression, we find, at least in the case of
the fishes, a further concentration of such groups with alternat-
ing C and N atoms. For, besides the pyrimidine and purine
derivatives of the nucleic acid part, there is also present the
basic protamine part. As has been explained above, this part
is composed largely of arginine, which, as the formula given
on p. 290 shows, contains the group —
NH2
NH = C-NH-CH2-. . .
1 Kossel, " Einige Bemerkungen iiber die Bildung der Protamine im
Thierkorper," Zeitschrift f. phys. Chemie, vol. xliv., 1905.
BIOCHEMISTRY OF THE SEXUAL ORGANS 299
These facts suggest that this special arrangement of alternating
C and N atoms is the chemical expression of the specific function
of the nucleus, and that this arrangement plays a special part
in bringing about the chemical processes which lead to growth
and to the new formation of living matter.
In the case of the other organic compound present in every
nucleus, which contains iron in organic combination, the
evidence that it plays an active part in the synthetic functions
of the nucleus is even more suggestive. It was shown by
Spitzer l that the oxidising enzymes which are present in every
cell are localised in the iron -containing constituent of the
nucleus, and Loeb concludes that the nucleus must be regarded
as the essential respiratory or oxidising organ of the cell.2
Oxidation processes are generally supposed to be necessary
only for the transformation of chemical energy into heat
and mechanical work. But they are, according to Loeb, equally
necessary for other more important and more general vital
processes, i.e. growth and cell division, which come to a stand-
still in the absence of oxygen. As a rule, cell division follows
upon the formation of nuclear material, especially chromatin
material, from the protoplasm of the cell. If we accept
Schmiedeberg's 3 view that in the living cell synthetic processes
may occur through the intervention of oxygen, we may conclude
that the oxygen which is required for the process of cell division
is probably needed for the synthesis of this nuclear material,
and, since the iron-containing organic compound present in the
nucleus has the power of bringing about oxidations, it would
follow that the synthetic functions of the nucleus are dependent
upon this compound. It must, however, be understood that
these considerations are still very hypothetical, and that other
biologists 4 deny that the nucleus is the respiratory or oxidising
centre of the cell.
The power possessed by the spermatozoon of bringing about
segmentation of the ovum has been attributed by some authors
1 Spitzer, " Die Bedeutung gewisser Nukleoproteide fur die oxydative
Leistung der Zelle," Pfluger's Archiv, vol. Ixvii., 1897.
2 Loeb, Dynamics of Living Matter, New York, 1906.
3 Schmiedeberg, " Uber Oxydationen und Synthesen im Thierkorper,"
Archiv f. experimentelle Pathologic u. Pharmakolvgie , vol. xiv., 1881.
4 See Verworn, Allgemeine Physiologic, 1909.
300 THE PHYSIOLOGY OF REPRODUCTION
to the action of ferments present in the spermatozoon. Fieri l
claimed to have extracted from the spermatozoa of Stron-
gylocentrotus lividus and Echinus esculentus a ferment, "ovulase,"
which induced segmentation of mature ova. Similar observa-
tions were made by Dubois 2 on Echinus, and by Winkler 3 on
Sphcerechinus granulosis and Arbacia pustulosa. The evidence
on which these authors base their conclusion is, however, not
very convincing, and the searching criticism to which their
observations were subjected by Gies,4 who repeated their ex-
periments, tends to show that their results were due to other
factors. Gies was unable to extract either from spermatozoa
or from fertilised ova any enzyme or zymogen capable of
causing development in mature ova of the same species.
Similarly Cremer 5 was unable to bring about fertilisation by
means of the press-juice obtained from spermatozoa (see p. 222).
Wolfgang Ostwald6 has determined the amounts of oxidising
ferments present in the ovaries and testes of toads, frogs, and
newts. The watery extracts of these organs had the power of
decomposing hydrogen peroxide with the formation of water and
oxygen, and of oxidising guaiaconic acid to guaiacum blue, so
that a blue colour appeared when these extracts were added to
an emulsion of guaiac resin. These reactions indicate the
presence of a catalase and of a peroxidase in the extracts of
the sexual glands. *Such ferments are present in many, if not
all, organs and tissue fluids, but a special significance is attri-
buted by Ostwald to their presence in the ova and spermatozoa,
because he found the spermatozoa to contain more catalase
and more peroxidase than the ova, and because the activity
1 Fieri, " Un Nouveau Ferment soluble : 1'Ovulase," Archives de Zooloyie
Experimental et Generate, vol. xxix., 1899.
2 Dubois, " Sur la Spermase et POvulase," Comptes Rendus de la Societe
de Biologic, vol. Hi., 1900.
3 Winkler (H.), " Uber die Furchung unbefruchteter Eier unter der Ein-
wirkung von Extraktiostoffen a. d. Spermata," Nachrichten der kgl. Gesell-
schaft der Wissenschaften zu Getting tn, Mathcmat.-Phys. Klasse, 1900.
4 Gies, " Do Spermatozoa contain an Enzyme having the Power of Causing
Development of Mature Ova ? " American Journal of Physiology, vol. vi., 1901.
6 Quoted from Loeb, Dynamics of Living Matter.
6 Wolfgang Ostwald, " Uber das Vorkommen von oxydativen Fermenten
in den reifen Geschlechtszellen von Amphibien und uber die Kolle dieser
Fermente bei den Vorgangen der Entwicklungserregung," Biochemische
Zeitschrift, vol. vi., 1907.
BIOCHEMISTRY OF THE SEXUAL ORGANS 301
of these ferments— especially the peroxidase — is increased when
the extracts of ova are mixed with the extracts of spermatozoa.
The development of the ovum after fertilisation is, according
to Ostwald, due to this activation of the oxidising ferments
inducing a chemical synthesis of nuclein substances, which form
a localised coagulum of a definite orientation, namely, the
astrosphere. According to the view of Fischer and Ostwald,1
which is, however, not accepted by other workers,2 the forma-
tion of the astrosphere initiates cell-division, and therefore the
development of the egg.
A very ingenious theory of the chemical mechanism of ferti-
lisation has been put forward recently by Loeb,3 as the result of
his work on artificial parthenogenesis. According to Loeb, the
development of the mature ovum is dependent upon two processes.
It is initiated by a cytolysis affecting the periphery of the cell.
This process, which is accompanied by the formation of a ferti-
lisation membrane, can be induced by any agent having a cyto-
lytic action, such as heat, ether, fatty acids, saponin, or the serum
of an animal of a different species. If this initial cytolysis is
allowed to proceed unchecked, the eggs, although they may
begin to divide, eventually undergo complete cytolysis. If, on
the other hand, the initial cytolysis is inhibited by suitable means,
such as treatment with potassium cyanide or immersion in
hypertonic sea- water containing oxygen, the eggs will develop in
the same way as if they had been fertilised by a spermatozoon.
If it be admitted that artificial parthenogenesis represents the
conditions governing fertilisation by a spermatozoon, then it
follows that a spermatozoon should contain two substances,
namely, a cytolysin, and a substance inhibiting the initial cyto-
lysis. The presence in the spermatozoon of a cytolysin can indeed
be proved. Extracts of the testis of a cock, or the dead semen
(killed by heating) of a starfish or a mollusc, will induce the
initial process of cytolysis in the eggs of a sea-urchin. The dead
semen of a sea-urchin, however, is quite inactive against the eggs
of a sea-urchin. This is in agreement with our knowledge of
1 Fischer and Ostwald, " Zur Physikalisch-Chemischen Theorie der
Befruchtung," PJliigtr's Archiv, vol. cvi., 1905.
2 See, for instance, Burrian, loc. cit.
3 Jacques Loeb, Die chemische Entwicklungserregung des tierischen
Eies, Berlin, 1909.
302 THE PHYSIOLOGY OF REPRODUCTION
the actions of cytolysins generally. The cytolysins present
normally in the serum or the cells of one animal are always
inactive against the cells of animals of the same species, and act
only against cells of animals of a different species. The explana-
tion of this fact is to be found, according to Loeb, in the diminished
permeability of the cells of one species towards the cytolysins
produced by the cells of animals of the same species, the so-called
auto-cytolysins.
Similarly the ovum of an animal is not permeable to the
cytolysins contained in the spermatozoon of an animal of the
same species. In order to bring about the development of the
mature ovum the auto-cytolysin must be carried bodily into the
egg. And that is the function of the motile spermatozoon.
APPENDIX1
More recent experiments on different insects 2 have confirmed
the fact that in these animals, as in birds, the main source of
the energy which is used up during development is fat. No
nitrogen is lost, but some of the protein material undergoes
partial oxidation, to uric acid, and may thus contribute to
the "energy of development." Whether the glycogen which
disappears during development serves as a source of energy
is doubtful. The chitin which is deposited in the cuticle of
insects is a compound built up mainly of carbohydrate-groups,
and it seems likely that these carbohydrate-groups are derived
from the glycogen, which thus contributes to the formation of
the cuticle. It is interesting to note that glycogen appears to
fulfil a similar function in the developing rabbit, where it also
contributes to the building up of the growing tissues.3 It
appears indeed to be a general law that carbohydrate material
is essential for growth.
1 See p. 281.
2 Farkas, loc. cit. ; Weinland, Zeitschr. /. Biologic, vol. xlvii., 1905;
vol. xlviii., 1907; vol. li., 1908; vol. Hi., 1909; Tangl, Pfliiger's Archiv,
vol. cxxx., 1909.
3 Lochhead and Cramer, loc. cit.
CHAPTER IX •
THE TESTICLE AND THE OVARY AS ORGANS OF
INTERNAL SECRETION
" Da muss sicli manches Rathsel losen,
Doch manches Riithsel kniipft sicli aucli."
— GOETHE.
THE principal evidence supporting the theory that the ovary
and testicle are organs of internal secretion is derived from the
experimental study of the effects produced, firstly, by removing
these organs, and, secondly, by transplanting them to abnormal
positions in the body. Experiments of such a kind clearly
demonstrate the influence of the ovary and testicle upon the
growth and development of the other generative organs, and
upon many of the secondary sexual characters. They indicate,
moreover, that the nature of this influence is chemical rather
than nervous. Certain further evidence, which is less satis-
factory in character, has been obtained from experiments on
the injection of ovarian and testicular extracts.
THE CORRELATION BETWEEN THE TESTIS AND THE
OTHER MALE ORGANS AND CHARACTERS
It has already been recorded (p. 239) that the removal of
the testes in adult life brings about a gradual atrophy of the
prostate gland. It has also been shown that this operation, if
performed prior to puberty, prevents the development of the
prostate, whereas division of the vas deferens and the abolition
of sperm production have no arresting influence.1 One-sided
castration produces no effect, the retention of a single testis
being sufficient to maintain the functional activity of both
1 Wallace (C ), " Prostatic Enlargement," London, 1907. It is shown also,
that vasotomy has no influence on the growth and activity of the prostate.
304 THE PHYSIOLOGY OF REPRODUCTION
prostate glands. Similiarly it has been stated that Cowper's
glands are probably dependent upon testicular influence for
their growth and activity (p. 240).
More remarkable is the close correlation that exists between
the testes and the secondary sexual characters of the male — that
is to say, those characters which are found only in the male sex,
but are not directly connected with the organs of generation.
Thus, it is notorious that castration before puberty in man
prevents the growth of hair on the face, arrests the development
of the male chest and pelvis, and preserves the high-pitched
voice of boyhood by hindering the growth of the larynx, while
at the same time it exercises a marked influence over the mental
characteristics.1 It is equally well known that at the time of
puberty, when the testes begin to assume their functional
activity, there is a corresponding development of the secondary
sexual characters, both in Man and in a large number of animals.
This correlation appears to be still closer in those animals in
which the increased testicular activity that takes place in the
breeding season is associated with a periodic development of
other sexual characters. Thus, in the male elephant the glands
on the side of the face emit a musky secretion during rut.2
Darwin,3 in elaborating his theory of sexual selection,
collected together numerous examples of secondary sexual
differences occurring in animals of various kinds. More recently
Cunningham, in a work upon Sexual Dimorphism, has cited
a number of further cases,4 in many of which the structural
1 According to Hikmet and Regnault (" Les Eunuques de Constantinople,"
Bull, et Mem. de la Soc. d' Anthropologie de Paris, vol. ii., 5th series, 1906),
the eunuchs of Constantinople have the following mental characteristics : —
They are avaricious, illogical, obstinate (i.e. cannot change their ideas), have
no judgment, accept information without proof ; are not cruel, but fond
of children and animals ; are faithful in their affections, but have no courage ;
their mental activity is very slight, and they are extremely fanatical. Senility
is premature, but the teeth are kept solid and white. For skeletal differences
in eunuchs, see below. 2 Of. page 305.
3 Darwin, The Descent of Man, Popular Edition, London.
4 Cunningham (J.T.)> Sexual Dimorphism in the Animal Kingdom,, London,
1900 ; " The Heredity of Secondary Sexual Characters in Relation to Hor-
nones," Arch. f. Entwick. Mech., vol. xxvi., 1908. See also Hegar, Korrelationem
der Keimdrusen und OeschUchtsbestimmung, 1893 ; and Selheim, " Zur Lehre
von den sekundaren Geschlechtscharakteren," Beitrdgczu Geburtsh. u. Gyncik.,
vol. i., 1898.
ORGANS OF INTERNAL SECRETION 305
peculiarities in question are shown to be closely correlated with
the essential organs of reproduction.
The effects of castration in the stag, for example, are dis-
cussed at some length by Cunningham, Morgan,1 and other
writers. If the testes are removed in quite immature animals
the antlers never develop, even the knobs failing to make an
appearance. If castration is performed in stags whose antlers
have just commenced to develop, these remain covered by skin,
forming the so-called peruke antlers, which are not shed or
renewed. If the operation is carried out after the complete
development of the antlers, these are shed prematurely and are
replaced in the next season by incomplete antlers with a tendency
towards peruke formation, and these, on being thrown off, are
not renewed. Partial castration in the immature stag is said
to result in a weaker horn formation ; but the effect is general, and
shows no restriction to the side on which the testis is wanting.2
The results of castration in the fallow deer have been in-
vestigated by Fowler,3 who summarises his results under five
headings : — (1) Complete castration at birth limits the horn
formation to the development of single dugs ; (2) Castra-
tion in mature life tends to produce asymmetry in the growth
of the horns ; (3) The antlers of castrated deer are often shed
prematurely if the operation is performed after they have lost
the velvet, but antlers which have grown after castration may
be retained for over two years ; (4) Incomplete castration
shortly after birth is followed by a weak development of the
antlers, which are otherwise normal ; (5) One-sided castration
may result in the abnormal or incomplete development of one
antler, the other antler being nearly normal. The last point
would seem to require confirmation.
In the prong-buck (Antilocapm americana), which is the
1 Morgan, Experimental Zoology, New York, 1907.
2 These statements are based chiefly upon the results of Caton's experi-
ments with Wapiti and Canadian deer (Caton, Antelope and Deer of Atneiica,
2nd Edition, New York, 1881. See also Holdich, " Exhibition of Antlers of
Deer showing Arrest of Development due to Castration"), Proc. Zool. Soc,,
1905. Some further examples of sexual correlation are given in Chapter I. of
this work, and Morgan, loc cit. Dr. Seligmann informs me that stags which
fail to grow antlers (i.e. occasional " sports") have well-developed testicles.
3 Fowler, " Notes on Some Specimens of Antlers of the Fallow Deer," &c.,
Proc. Zool. Soc., 1894.
U
306 THE PHYSIOLOGY OF REPRODUCTION
only hollow-horned Ruminant that periodically sheds its horns,
the effects of castration are also quite distinct. The horns, instead
of rising vertically as in normal individuals, curve forwards
from the roots, and then bend downwards and backwards so
as to terminate in incurved points in the close vicinity of the
eyes. The anterior tine is almost completely suppressed.
The horn-sheath is never shed, and as a consequence a com-
posite sheath is developed, and this seems to go on growing as
long as new sheaths are formed from the horn-core.1
It is interesting to note that in the eland, in which both
sexes possess horns, the development of these structures is not
appreciably affected by castration.2 A similar statement may
be made about horned cattle, in which (in common with other
cattle) castration in early life produces changes in the general
proportions of the body.
In the sheep, also, castration during immaturity brings about
changes in the bodily conformation. Thus, in breeds in which
the males only are horned, the skulls of the wethers may
resembles the females rather than the males.1 Differences in
the form of the body have also been noted in eunuchs and other
castrated animals. Thus, the bones of the limbs tend to be
longer than the normal, producing a condition of gigantism.
This is due to an arrest in the ossification of the epiphyses (which
is one of the effects of castration). The same phenomena have
been described in castrated guinea-pigs, oxen, capons, and various
animals.3
It is well known that caponisation or the removal of the
1 Pocock, "The Effects of Castration on the Horns of the Prong-buck,"
Proc. Zool. Soc., 1905. It is to be noted that horns are occasionally present
in the female prong-buck.
2 Seligmann, " Exhibition of a Skull of a Domestic Sheep which had been
Castrated when Young," Proc. Zool. Soc., 1906. Changes in conformation as
a result of early castration have also been described in other animals.
3 Lannois and Eoy, " Des Relations qui existent entre I'l^tat des Glandes
genitales males et le Developpement du Squelette"; and Poncet, " De
1'Influence de la Castration sur le Developpement du Squelette," C. R. de la
Soc. de BioL, vol. lv., 1902. See also Pittard, C. E. de I'Acad. des Sciences,
vol. cxxxix., 1904), who gives statistics showing that there is often an increase
in size in eunuchs, especially in the legs. For accounts of other anatomical
differences in eunuchoid persons, see Duckworth, Jour, of Anat. and Phys., vol.
xli., 1906, and Tandler and Gross (Arch. f. Entwick.-Mech., vol. xxvii., 1909).
The latter authors discuss the general effects of castration on the organism.
ORGANS OF INTERNAL SECRETION 307
testes in fowls arrests the development of the comb and spurs
and other secondary male characters which are normally present
in the cock. Other instances of the effects of castration are
briefly referred to by Darwin.1
Secondary sexual characters, however, are not always
correlated with the essential organs of reproduction. For
example, castration in the horse does not arrest the develop-
ment of the withers — the gelding, in this respect, resembling
the stallion rather than the mare, in which the withers are lower.2
In Arthropods the correlation between the secondary sexual
characters and the generative glands appears to be far less close
than it is among Vertebrates. Thus, Oudemans 3 showed that
the removal of the testes from the male caterpillar of Ocneria
dispar had no influence on the development of the secondary
male characters, these being normal. Kellogg 4 performed a
similar experiment on the caterpillar of the silkworm moth and
obtained a like result. Crampton 5 grafted the heads of cater-
pillars of one sex upon the bodies of individuals of the opposite
sex, and found that the generative organs had no influence
upon the development of the secondary sexual characters of the
transplanted heads. Moreover, Meisenheimer 6 found that in
caterpillars artificially made hermaphrodite (by transplanting
ovaries into males or testes into females) the original males
always developed into butterflies with typical secondary male
characters in spite of the fact that living ovaries were present,
while the original females always developed into normal female
butterflies. The sexual instincts were also unmodified by the
presence of the grafted gonads.
In spider crabs attacked by Sacculina the gonads disappear,
1 Darwin, loc. cit. Selheim (Beitrdge zur Geburtshulfe und Gyndk., vol. i.,
1898, and vol. ii., 1899), states that there is an increase in the size of the skull,
pelvis, and leg-bones in castrated cocks.
2 Wallace, Farm Live-Stock of Great Britain, 4th Edition, London, 1907.
3 Oudemans, "Falter aus Castriten Raupen," Zool. Jahrbiicher, vol. xii.,
1899.
4 Kellogg, " Influence of the Primary Reproductive Organs on the Second-
ary Sexual Characters," Jour, of Exper. Zool., vol. i., 1904.
5 Crampton, " An Experimental Study upon Lepidoptera," Arch. f.
Entwick.-Mechanik, vol. vii., 1898.
6 Meisenheimer, Exper imentelle Studien zur Soma- und Geschlechts-
Differenzierung , Part I., Jena, 1909.
308 THE PHYSIOLOGY OF REPRODUCTION
and in the total absence of the testis secondary sexual characters
of the female type are found in a large percentage of cases ; but
this change in the direction of the opposite sex may set in prior
to the complete disappearance of the testes. The change is
manifested in the appearance of the egg-bearing abdominal
sac appendages, which have no representatives in the male.1
Potts states that in the hermit crab infected by a similar Pelto-
gaster, the modifications of the male which occur are of the same
type, and are maintained after the atrophy of the testis, and
cannot be necessarily consequent on the presence of a secretion
of the testis.2
In both these cases it is suggested that the modifications
which take place are brought about independently by changes in
the general metabolism.
In the male common shore crab it was found that the testis
underwent very little diminution after infection by Sacculina,
but that the male approximated to the female type. The change,
however, was less marked than in the cases referred to above,
in which parasitic castration was almost or quite complete.3
It would appear, therefore, that whereas many of the
secondary sexual characters are closely associated with the
presence of the genital glands, there are others which develop
independently of any influence from the organs of reproduction.
Brown-Sequard 4 seems to have been the first definitely to
put forward the view that the testis exercises its influence upon
the metabolism through an internal secretion elaborated by it.
He based his conclusion to a large extent upon the beneficial
effects which he believed to accrue from the administration of
testicular extracts. These extracts were supposed to possess
invigorating properties, and could be usefully employed in cases
of deficiency of testicular substance, or in old age, when the
testes lose their functional activity. It is not unlikely that
1 Smith (Geoffrey), " Ehizocephala, Fauna and Flora of the Gulf of Naples,"
Monograph xzir., Berlin, 1906.
2 Potts, " The Modification of the Sexual Characters of the Hermit Crab,
caused by the Parasite Peltogaster," Quar. Jour. Micr. Sci., vol. 1., 1SOG ; and
"Some Phenomena Associated with Parasitism," Parasitology, vol. ii., 1909.
3 Potts, " Observations on the Changes in the Common Shore Crab caused
by Sacculinu," Proc. Camb. Phil. Soc., vol. xv., 1909.
4 Brown-Sequard, " Du Kole physiologique et therapeutique d'un Sue
extrait de Testicules," Arch, de Phys., 1889.
ORGANS OF INTERNAL SECRETION 309
some of the effects which Brown-Sequard attributed to the
use of the extract were in reality due to suggestion.
Poehl l claims to have prepared from the testis a substance
having the chemical composition represented by the formula
C5HHN2. He believes this substance, which he calls spermine,
to be the active principle of Brown-Sequard's testicular extract,
stating that it has a beneficial influence over the metabolism of
the body and acts as a physiological tonic. (See p. 285.)
Zoth,2 and also Pregel,3 state that they have obtained
evidence by ergographic records of the stimulating action of
testicular extracts upon the neuro-muscular apparatus in the
human subject. They are of opinion that the injection of
such extracts results in a decrease of nervous and muscular
fatigue, arid at the same time diminishes the subjective fatigue
sensations.
The composition and physiological properties of testicular
extract have also been investigated by Dixon,4 who found it to
contain proteins, organic substances unaltered by boiling, and
inorganic salts. Nucleoprotein was especially plentiful. In-
jection into the circulation caused a fall of blood pressure due
chiefly to cardiac inhibition, but no very striking or interesting
results.
Walker 5 appears to be dubious about the efficacy of testicular
medication, stating that the injection of fluid extract into
castrated dogs had no effect in arresting the atrophy of the
prostate gland (cf. de Bonis, see Chapter VII., p. 239). It is
possible, however, that the " active principle " of the testicular
secretion was destroyed in the preparation of the extract, and
1 Poehl, " Weitere Mitteilungen iiber Spermin," Berliner klin. Wochen-
schrift, 1891.
2 Zoth, "Zwei ergographische Versuchsreihen iiber die Wirkung orchi-
tischen Extractes," Pfliiger's Archiv, vol. Ixii., 1896.
3 Pregel, " Zwei weitere ergographische Versuchsreihen," &c., Pfliiger's
Archiv, vol. Ixii., 1896.
4 Dixon, "A Note on the Action of Poehl's Spermine," Jour, of Phys.,
vol. xxv., 1900 ; " The Composition and Action of Orchitic Extracts," Jour,
of 'Phys., vol. xxvi., 1901. According to Hervieux, the interstitial gland of
the testis contains a ferment which splits neutral fats, and converts dextrin,
maltose, and glycogen into glucose but has no action on lactose (C. R. de la
Soc. BioL, vol. lx., 1906).
5 Walker (G.), " Experimental Injection of Testicular Fluid," &c., Johns
Hopkins Hospital Bulletin, vol. xi., 1900.
310 THE PHYSIOLOGY OF REPRODUCTION
that the constant administration of fresh testicular substance
might have led to a different result.
Bouin and Ancel x have shown in the horse and other animals
that when the vasa deferentia are ligatured the spermatogenetic
tissue of the testis ceases to be functional and gradually under-
goes degeneration, while the interstitial cells remain unaffected.
They point out, further, that those cells have a distinctly
glandular appearance, and that their presence suffices for the
development of the secondary sexual characters. Consequently
they draw the conclusion that the testis is an organ producing
an internal secretion which is elaborated by the interstitial cells
and not by the spermatogenic tissue. These investigators state,
further,2 as a result of a series of experiments upon guinea-pigs,
that the subcutaneous injection of extract prepared from the
interstitial tissue of the testis arrests the effects which castration
otherwise would produce upon the rest of the generative system
and upon the skeleton.3 Their results, therefore, differ from those
of Walker. In another paper Bouin and Ancel 4 state that the
injection of similarly prepared testicular extract in guinea-pigs
tends to promote growth. In the horse they found that the
development of the interstitial gland substance of the adult
coincided with the first occurrence of spermatogenesis ; but that
there was also a foetal interstitial gland, which disappeared at the
end. of gestation, and a slightly developed gland composed of
xanthochrome cells, which was only found in the immature
animal.5
1 Bouin and Ancel, " Recherches sur les Cellules interstitielles du Testicule
des Mammiferes," Arch, de Zool. Exper., vol. i., 4th series, 1903.
2 Bouin and Ancel, "Action de 1'Extrait de Glande interstitielle du
Testicule," &c., C. R. de VAcad. des Sciences, vol. cxlii., 1906.
3 Castration in early life, as already mentioned, is said to lead to a
prolonged retention of the cartilaginous unions between the bones, especially
in those of the limbs.
4 Bouin and Ancel, " Sur 1'Effet des Injections de 1'Extrait de Glande
interstitielles du Testicule sur la Croissance," C. R. de la Soc. de Biol.,
vol. Ixi., 1906.
6 Bouin and Ancel, " La Glande interstitielle du Testicule chez le Cheval,"
Arch, de ZooL Exper., vol. iii., 4th series, 1905. According to Lecaillon
the interstitial tissue in the mole's testis is functionally active during the
breeding season, when the testis is sixty-four times larger than during the
resting period. (" Sur les Cellules interstitielles du Testicule de la Taupe con-
siderees en dehors de la Periode de Reproduction,'' C. R. de la Soc. de Biol.,
vol. Ixvi., 1909).
ORGANS OF INTERNAL SECRETION 311
Shattock and Seligmann l also have performed experiments
on the results of occluding the vasa deferentia in Herdwick
rams and in fowls. The animals operated upon acquired full
secondary characters. The authors suppose, therefore, that the
development of these characters is not brought about by rue tn- ~
bolic changes induced by a nervous reflex arising from the
function of sperm ejaculation.
Foges 2 has described the effect of removing the testes of
fowls and transplanting them to abnormal positions in the
body cavity. In the successful experiments it was found that
the presence of functional transplanted testes exercised the
same influence over the development of the secondary sexual
characters as testes growing in the normal position, and that
the appearance of " capon " characters was averted, the
comb, wattle, spurs, &c., being developed as in uncastrated
cocks. Foges concludes that the testes are organs of in-
ternal secretion, and control the development of the male
characters.
Shattock and Seligmann have also described the effects of
testicular transplantation and incomplete caponisation in fowls.
In certain cases the testes are stated to have broken up during
the operation, so that minute fragments were retained, some-
times being left in the normal position, and sometimes becoming
dislocated and attached to the adjacent viscera or to the ab-
dominal wall. Although these pieces of testicular substance
continued to produce spermatozoa, they were virtually ductless
glands. In such cases the secondary sexual characters of the
cock developed to a varying extent which seemed to depend
upon the amount of testicular substance left behind. " One
must regard the external character of maleness as a quantity
which varies proportionately with the amount of gland tissue
present."
1 Shattock and Seligmann, " Observations upon the Acquirement of
Secondary Sexual Characters, indicating the Formation of an Internal Secre-
tion by the Testicle," Proc. Roy. Soc., vol. Ixxiii., 1901. The same investi-
gators also attempted to obtain further evidence by grafting together two
cocks, one castrated and the other normal, but these experiments were
unfortunately a failure, one of the birds always dying after a short time,
Trans. Path. Soc., vol. xlvi., 1905.
2 Foges, "Zur Lehre der secundaren Geschlechtscharaktere," Pfluger's
Archiv, vol. xciii., 1903.
312 THE PHYSIOLOGY OF REPRODUCTION
According to Loewy,1 the injection of testicular substance
into young capons causes the development of normal male
skeletal characters, as well as a better growth of the comb, &c.
Furthermore, Walker 2 states that, in two experiments in which
he injected saline extract of cocks' testicles into two hens daily
for several months, the combs and wattles grew in size and
became more brightly coloured, reaching a maximum in five
months. When the injections were discontinued, the combs and
wattles underwent shrinkage and eventually became reduced
almost to their original condition. These experiments are of
interest, but they would seem to require confirmation before
the conclusion can definitely be drawn that the testicular
extract exerted an influence upon the sexual characters of the
hens, since the combs and wattles of fowls are normally subject
to periodic growth which may vary with the individual.
It is stated that an imperfectly descended testicle (i.e. a
testicle which has failed to descend properly from the abdominal
cavity into the scrotal sac) in Man, notwithstanding the fact
that it may be without any spermatogenic function, is never-
theless of the greatest benefit to its possessor in virtue of its
influence over the metabolism. " The secondary sexual
characters are a far more exact measure of the value of the
testicular tissues than are the presence of spermatozoa in
the external secretion. It may almost be said that a man's
male plumage is in direct proportion to the weight or amount
of testicular tissue present/' 3
Perhaps the most conclusive evidence so far adduced in
support of the theory that the testis produces an internal secre-
tion is that supplied by Nussbaum 4 as a result of his experi-
ments upon frogs. At the approach of the breeding season
there is formed in the male frog a thickened pad of skin on the
first digit of each fore limb associated with an increased muscular
1 Loewy, "Neuere Untersuchungen zur Physiologic der Geschlechts-
organe," Ergebnisse der Phys., vol. ii., 1903.
2 Walker (C. E.) "The Influence of the Testis upon the Secondary Sexual
Characters of Fowls," Proc. Roy. Soc. Med., vol. i., 1908.
3 Corner, Diseases of the Male Generative Organs, Oxford, 1907. See
also Me Adam Eccles, The Imperfectly Descended Testis, London, 1903.
4 Nussbaum, " Innere Sekretion und Nerveneinfluss," M erkel and Bonnet,
Ergeb. der Anat. und Entwick., vol. xv., 1905.
ORGANS OF INTERNAL SECRETION 313
development in the fore arm. This modification is preparatory
to the act of copulation, when the male frog uses its arms in
embracing the female, and so assists in pressing out the eggs
from the oviduct (see p. 22). If the male frog be castrated,
the pad is not formed and the muscles fail to develop. Nuss-
baum found that, if pieces of testis from another frog were grafted
into the dorsal lymph sac of a frog previously castrated, the
secondary sexual characters of the latter developed just as in a
normal frog. The transplanted testes, however, after exerting
their influence in the way described, underwent a gradual ab-
sorption.
Nussbaum states, further, that when the nerves supplying
the first digit were severed, the pad did not develop, this opera-
tion being performed on a normal frog. Similarly if the nerves
supplying the clasping muscle of the fore arm were severed, the
enlargement did not occur. He concludes, therefore, that the
internal secretion formed in the testis has a specific action upon
certain local groups of ganglion cells, and that the nerves passing
from these to the fore arm and digit convey a stimulus which
induces the growth of the muscle and that of the thickened pad.
In support of the view that the testis exerts its influence upon
the metabolism (at least partially) through the medium of the
nervous system, Nussbaum cites an observation of Weber,
according to whom an hermaphrodite finch, having an ovary on
one side of the body and a testis on the other, showed the charac-
teristic female coloration on the ovarian side and the male plumage
on the side of the testis.
Nussbaum 's conclusion has been controverted by Pfliiger,1
who points out that in other cases the apparent effect of section
of nerves is due to loss of sensibility in the parts affected, in con-
sequence of which the tissues are not guarded from injury, and
further, that the secondary sexual characters of animals are
usually arranged symmetrically. The effect produced by one-
sided castration is general rather than local, and the operation
has little or no influence in destroying the symmetry of the sexual
characteristics (cf,, however, Fowler's statement about fallow
deer, which appears to be exceptional). It is probable, therefore,
1 Pfliiger, "Ob die Entwicklung der sekundaren Geschlechts-charaktere
vom Nervensystem abhangt?" Pfluger's Archiv, vol. cxvi., 1907.
314 THE PHYSIOLOGY OF REPRODUCTION
that Pfliiger is correct in supposing that the internal secretion
of the testis acts as a direct stimulus upon the cells of the frog's
arm, and so induces the development of the sexual pad and the
hypertrophy of the muscle.1
There is some evidence to show that, after one-sided castration,
the remaining testis is capable of undergoing a compensating
hypertrophy.2 If this is so, it affords an additional indication
that the testis is an organ of internal secretion.
THE CORRELATION BETWEEN THE OVARY AND THE
OTHER FEMALE ORGANS AND CHARACTERS
It has long been known that the ovary, like the testis, exerts
a profound influence over the metabolism, and that the ex-
tirpation of this organ, no less than castration in the male,
leads to very distinct results. In the human female double
ovariotomy, if carried out before puberty, besides preventing
the onset of puberty and the occurrence of menstruation, produces
noticeable effects on the general form and appearance, as may
be seen in adult women in semi-barbarous parts of Asia, where the
natives perform this operation upon young girls. Such women
are said to be devoid of many of the characteristics of their sex,
and in certain cases to present resemblances to men.
In some female animals, also, the removal or incomplete de-
velopment of the ovaries has been said to lead to the appearance
of male characters. For example, Rorig 3 records three cases in
which female deer possessed horns, and were found upon exami-
nation to show abnormalities in the ovaries. Darwin 4 also states
that female deer have been known to acquire horns in old age.5
1 See also Nussbaum, " Hoden und Brunstorgane," &c., Pfluger's Arch.,
vol. cxxvi., 1909. For further references to the literature of testicular
transplantation, see Boruttau, " Innere Sekretion," Nagel's Handbuch der
Physiologic des Menschen, Braunschweig, 1906.
2 Ribbert, " Beitrage zur kompensatorischen Hypertrophie," &c., Arch. f.
Entwick.-Mechanik, vol. i., 1894.
3 Rorig, " Ueber Geweihentwickelung," &c., Arch.f. Entwick.-Mechanik,
vol. x., 1900.
4 Darwin, Variation in Animals and Plants, Popular Edition, London,
1905.
6 Smith (F.) (Veterinary Physiology, 3rd Edition, London, 1907) states that
female cats, whose ovaries have been removed while young, acquire a head of
ORGANS OF INTERNAL SECRETION 315
Better instances of this kind of phenomenon have been
recorded from among poultry, game birds, and ducks, which,
on growing senile, have been observed to acquire some of
the secondary male characters. Darwin * refers to the case
of a duck which, when ten years old, assumed the plumage of
the drake. He also mentions an instance of a hen which in old
age acquired the secondary sexual characters of the cock.
Hunter 2 described a case of a hen pheasant which had male
plumage correlated with an abnormal ovary, and many other
such instances have been recorded. Gurney 3 states that the
assumption of male plumage is frequently (but not invariably)
associated with barrenness in female gallinaceous birds but not
as a rule in passerine birds. The phenomenon has been observed
in black grouse, capercaillie, wild duck, widgeon, merganser, and
various other species belonging to different orders. On the
other hand, Gurney records instances of a hen chaffinch with
male plumage and an unlaid egg, a hen redstart with male
plumage and a number of developing eggs, as well as similar
cases of hen pheasants. The male plumage may be only tem-
porarily assumed. Further examples of the assumption of male
plumage by hen birds are recorded by Shattock and Seligmann,4
who describe the phenomenon under the name of allopterotism.
Some of these cases are regarded as of the nature of partial
hermaphroditism. It would appear possible that the secondary
male characters are normally latent in the female, and that the
ovaries exert an inhibitory influence over their development. On
the male type (with well-developed tissues in the jowl, the exact converse
occurring in castrated males). Herbst, who also discusses this question
(Formative Reize in der Tierischen Ontogenese, Leipzig, 1901), expresses the
belief that the gonads in either sex exercise a definite inhibitory influence,
preventing the appearance of the secondary sexual characters of the
opposite sex.
1 Darwin, loc. cit.
2 Hunter, "Account of an Extraordinary Pheasant," Phil. Trans.,
vol. Ixx., 1780.
3 Gurney, " On the Occasional Assumption of Male Plumage by Female
Birds," Ibis, vol. vi., 5th series, 1888.
.4 Shattock and Seligmann, "An Example of True Hermaphroditism in
the Common Fowl, with Remarks on the Phenomena of Allopterotism,"
Trans. Path. Soc., vol. Ivii., 1906. "An Example of Incomplete Glandular
Hermaphroditism in the Domestic Fowl," Proc. Roy. Soc. Med., Path. Section
vol. i. (November), 1907.
316 THE PHYSIOLOGY OF REPRODUCTION
the other hand, there is no clear evidence that castration in the
male animal leads to the assumption of female characters, ex-
cepting in a negative sense (i.e. excepting in so far as it inhibits
the development of male characters).
The operation of complete ovariotomy is impracticable in
birds owing to the diffuse condition of the ovary and the close
proximity of the vena cava, and in de-sexing pullets (or con-
verting them into " poullardes ") the usual practice is to remove
a portion of the oviduct or destroy in some other way its func-
tional relation with the ovary.1 This operation is believed to
favour growth and fattening, but the result may be due simply
to the fact that the albumen and the other products of oviducal
secretion are no longer produced.
According to Brandt,2 the absence of a functional oviduct
may be correlated with male characters and a normal ovary,
this being stated to be the case in Rutidlla phosnicurus, but such
a fact seems on the face of it unlikely excepting on the assumption
that a partial hermaphroditism existed.
Ovariotomy performed subsequently to puberty in women
produces less marked results than when carried out in early
life. The most noticeable effect is the cessation of menstruation,
and this is sometimes accompanied by an atrophy of the breasts
and a tendency towards obesity.
Most authorities are agreed that the uterus undergoes atrophy
after the removal of the ovaries in adult life, and that castration
in children and young animals arrests the development of the
uterus.3 These results are usually ascribed to the absence of
ovarian influence, though a few authors seem disposed to dissent
from this view (see below, p. 345). Thus, Hofmeir 4 and Benkiser 5
1 Wright, The New Book of Poultry, London, 1902. Laycock, Nervous
Diseases of Women, London, 1840.
2 Brandt, " Anatomisches und Allgemeines iiber die sogenannte Hahnen-
fedrigkeit und iiber anderweitige Geschlechtsanomalien bei Vogeln," Zeitschr.
f. wiss. Zool., vol. xlviii., 1889.
3 Kehrer, Beitrdge zur Klin, und Exper. Geburtskunde, Giessen, 1877.
Hegar, Die Kastration der Frauen, Leipzig, 1878. Selheim, " Die Physiologic
der Weiblichen Genitalien," NageVs Handbuch der Physiologic des Menschen,
vol. ii., Braunschweig, 1906. This article contains further references.
4 Hofmeir, " Ernahrung und Riickbildungsvorgange bei Abdominal-
tumoren," Zeitsch. f. Geburtsh. u. Gynak., vol. v.
5 Benkiser, Verhandl. d. Deutsch. Gesell.f. Gynak., Fourth Congress, 1891.
ORGANS OF INTERNAL SECRETION 317
ascribe the degenerative changes to an insufficiency in the blood
supply consequent upon the operation of removal, while Sokoloff l
and Buys and Vandervelte 2 have supposed these changes to be
due to a severance of nerves passing to the uterus.
In a series of experiments performed recently 3 upon the"
effects of ovariotomy in rabbits, it was found that the extent
to which the degenerative process was carried was roughly
proportional to the time which had elapsed between the opera-
tion and the killing of the animal. After an interval of six and
a half months the uterus was found to be in a condition of pro-
nounced fibrosis and to contain no glands. The epithelium
was much attenuated, and the muscle fibres were broken up.
A few small capillaries, however, could still be seen in the
stroma. The Fallopian tubes also underwent atrophy. In
other experiments in which the ovaries were removed from
very young immature rabbits, which were killed after they
had grown up, it was found that the uteri, although they had
undergone slight development, were quite infantile, being no
larger than those of rats. The Fallopian tubes were affected
similarly. In all these experiments great care was taken to
avoid interference with the blood supply to the uterus, the
uterine branches of the pelvic vessels and the anastomotic branch
of the ovarian artery being left uninjured. Furthermore, in
certain other cases in which hysterectomy was performed instead
of ovariotomy, and which, therefore, may be regarded as con-
trols to the first series of experiments, the extirpation of the
uterus had no arresting influence on the growth and nutrition of
the ovaries (see p. 348).
Other and more conclusive evidence in support of the theory
that the ovary is an organ of internal secretion is supplied by the
results of various attempts to transplant ovaries. The cases of
Morris, Glass, Dudley, and Cramer, who transplanted ovaries
from one woman to another, are described below in discussing
the causes of the menstrual function (p. 331).
1 Sokoloff, " Ueber den Einfluss der Ovarienextirpation auf Structur-
veranderungen des Uterus," Arch. f. Oynak., vol. li., 1896.
2 Buys and Vandervelte, " Kecherches Experimentales sur les lesions
consecutives a 1'Ovariotornie Double," Arch. Ital. de Biol., vol. xxi., 1894.
3 Carmichael and Marshall, " The Correlation of the Ovarian and Uterine
Functions," Proc. Roy. Soc. B., vol. Ixxix., 1907.
318 THE PHYSIOLOGY OF REPRODUCTION
Knauer l has described experiments upon rabbits in which
he removed the ovaries from the normal position and grafted
them upon the mesometrium or between the fascia and the
muscle of the abdominal wall. He found that they could be
successfully implanted on both peritoneum and muscle, but
that some portion of the grafted ovary invariably died. The
FIG. 67.— Transverse section through rabbit's uterus after ovariotomy,
showing degenerative changes. (From Blair Bell, British Medical
Journal and Trans. Royal Society of Medicine. )
rest, however, remained functionally active, and continued to
produce ova which were capable of being fertilised. Knauer
states that whereas castration in female rabbits produced a
premature menopause, the uterus undergoing atrophy, this
result was prevented by a successfully transplanted ovary.
Knauer also experimented upon dogs and obtained similar
results.
1 Knauer, " Die Ovarien-Transplantation, Experimentelle, Studie," Arch.f.
Gynak., vol. lx., 1900.
ORGANS OF INTERNAL SECRETION
319
Grigorieff,1 Ribbert,2 and Rubinstein 3 carried out experi-
ments upon rabbits which confirmed those of Knauer, the
ovaries being transplanted in various abnormal positions.
Grigorieff also records two cases in which ovaries were success-
fully transplanted from one individual to another (heteroplastie-
transplantation). Ribbert found, in his experiments, that
FIG. 68.— Transverse section through bitch's uterus 9| months after
ovariotomy. (From Blair Bell, British Medical Journal and Trans.
Royal Society of Medicine.)
during the first month after transplantation the peripheral part
of the grafted ovary remained unaltered, but the central part
became transformed into connective tissue. At a later period,
however, the central portion was again found to contain follicles.
This fact is attributed to the conditions of increased nutrition
which Ribbert supposed to prevail when the ovaries had been
1 Grigorieff, "Die Schwangerschaft bei Transplantation der Eierstocke,"
Central, f. Gynak., vol. xxi., 1897.
2 Ribbert, " Uber Transplantation von Ovarien, Hoden, und Mamma,"
Arch. f. Entwick.-Mechanik, vol. vii., 1898.
3 Rubinstein, "Extirpation beiden Ovarien," St. Petersburg Mediz.
Wochenschr., 1899.
320 THE PHYSIOLOGY OF REPRODUCTION
transplanted for a sufficiently long period to admit of their
having acquired better vascular connections.
Halban l found that the uterus and mammary glands of
guinea-pigs from which the ovaries had been removed shortly
after birth, remained undeveloped ; but, if the ovaries were
removed from the normal position and grafted underneath
the skin, the other generative organs developed normally.
Limon,2 working upon rabbits, grafted ovaries beneath the
muscle layers of the abdominal wall and on to the peritoneum
of the same individuals. The follicles showed a tendency to
degenerate, but the interstitial cells, after a short period of
starvation, subsequently recuperated and acquired a con-
dition of perfect vitality. Limon states that he found no sign
of atrophy in the uterus after the transplantation of the ovaries
to an abnormal position.
Carmichael 3 has recorded some success from experiments in
1 Halban, " Ueber den Einfluss der Ovarien auf die Entvvickelung des
Genitales," Monatschr.f. Geburtsh. u. Gyndk., vol. xii., 1900.
2 Limon, "Observations sur 1'^tat de la Glande Interstitielle dans les
Ovaries Transplantds," Jour, de Phys. et de Path. Gen., vol. xvi., 1904.
3 Carmichael, "The Possibilities of Ovarian Grafting in the Human
Subject," &c., Jour, of Obstet. and Gyncec., March, 1907. Ovarian trans-
plantation in different species of animals has also been carried out by
Herlitzka (" Recherches sur la Transplantation des Ovaries," Arch. Ital. de
Biol., vol. xxxiv., 1900), Fok (" La Graffe des Ovaries en Relation avecQuelques
Questions de Biologic," Arch. Itzl. de Biol., vol. xxxiv., 1900), Schultz
(" Transplantation der Ovarien auf Mannliche Tiere," Central./. All. Path. u.
Path. Anat., vol. xi., 1900), Guthrie (" Successful Ovarian Transplantation
in Fowls," Internal. Congress of Phys., Heidelberg, 1907, Abstract in Zeit.
f. Phys., vol. xxi., 1907; "Further Results of Transplantation of Ovaries in
Chickens," Jour. ofExp. Zool , vol. v. , 1908). Schultz and other investigators,
without reference to the ovarian secretion theory, grafted the ovaries of
guinea-pigs on to the bodies of males and recorded some success. Herlitzka
also grafted the ovaries of guinea-pigs on to other individuals (heteroplastic
transplantion), some females and some males. Only one experiment was at all
successful, the ovary being transplanted on to a female. Fok was successful
with several heteroplastic grafts in rabbits, and even succeeded in inducing
pregnancy in an animal with a transplanted ovary. Guthrie' s experiments
were upon fowls. He states that the ova in the heteroplastically transplanted
ovaries were influenced by the " foster mother" (i.e. the birds into whom they
were grafted), since the offspring which resulted from fertilising these ova par-
took of some of the foster-mother's characters. For a few further references
see Marshall and Jolly, " Results of Removal and Transplantation of Ovaries,"
Trans. Roy. Soc. Edin., vol. xlv., 1907, and " Heteroplastic Transplantation, ''
&c., Quar. Jour. Exp. Phys., vol. i., 1908 ; and Sauve", Les Greffes Ovariennes,
Paris, 1909.
ORGANS OF INTERNAL SECRETION 321
which the ovaries of rabbits were transplanted on to abnormal
positions in the same individuals (homoplastic transplantation),
but there is no evidence in those cases that the grafted ovaries
had any influence in preventing the degeneration of the uterus.
FIG. 69. — Section through ovary of rat after transplantation on to peritoneum,
showing ovum, normal follicles, and follicles which have undergone
cystic degeneration. (From Marshall and Jolly.)
The present writer also, working in conjunction with Dr.
Jolly,1 carried out a series of experiments upon rats in order to
determine whether any histological changes occurred in the
1 Marshall and Jolly, loc. cit.
X
THE PHYSIOLOGY OF REPRODUCTION
uterus after transplanting the ovaries to new situations. Other
experiments were undertaken in which the ovaries were simply
removed without being transplanted. The rats were killed at
FIG. 70. — Section through ovary of rat after transplantation on to peritoneum,
showing corpora luteum and small follicle with ovum. (From Marshall
and Jolly.)
intervals varying from one to fourteen months after the opera-
tion. In the control animals pronounced fibrosis or other
atrophic appearances were always found in the uterus. On the
ORGANS OF INTERNAL SECRETION
323
other hand, in those animals in which ovaries had been success-
fully transplanted on to abnormal positions (such as on to the
ventral peritoneum or into one of the kidneys) the uterus was
found undegenerated. If, however, the ovarian graft failed to
\)
FIG. 71. — Transverse section through normal uterus of rat.
(Cf. Figs. 72 and 73. From Marshall and Jolly.)
" take/' or was only partially successful, the uterus presented
undoubted signs of degeneration. In the cases of transplanta-
tion from rat to rat, as in homoplastic transplantation, uterine
degeneration was found to be arrested by a successful ovarian
graft.
324 THE PHYSIOLOGY OF REPRODUCTION
The successfully transplanted ovaries exhibited all the
characteristic histological features of normal ovarian tissue,
excepting that the germinal epithelium was invariably absorbed
after the lapse of a short interval. In some cases a certain
amount of degenerative change took place, only certain ele-
ments of the tissue being recog-
nisable after the lapse of several
months ; thus, the stroma might
present its normal appearance
while the follicles had disap-
peared, or the greater part of
the graft might be composed of
luteal tissue alone. It was also
observed that the successfully
transplanted ovaries underwent
the same cyclical changes as
normal ovaries. Thus, in animals
killed shortly before the com-
mencement of the breeding
season, large follicles were found
in the grafts, while at a later
period corpora lutea were present,
showing that ovulation had
occurred in the transplanted
ovaries. In one case, a homo-
plastic graft was found to be
normal after fourteen months,
while a normal heteroplastic
graft was composed entirely
of healthy ovarian tissue (with
follicles and ova) after six
months. In these experiments
the ovaries were grafted into the substance of the kidneys. '
Homoplastic transplantation was found to be more easily
accomplished than heteroplastic transplantation. This result
could hardly be ascribed to increased difficulties in the per-
formance of the latter operation, since the technique was
identical in each case. Furthermore, our successes in hetero-
plastic transplantation were usually obtained in experiments
FIG. 72. — Transverse section
through uterus of rat after
ovariotomy, showing degener-
ative changes. (Of. Figs. 71
and 73. From Marshall and
Jolly.)
ORGANS OF INTERNAL SECRETION 325
in which two rats from the same litter were known to have been
employed, so that the ovaries were grafted into whole sisters,
but we were not sure of the relationship in every case.
**r.;.\.
" ', -'~t-
f; .;• ... •,*'• :-:•
:%^im
3'/,--;'^ - -^ATo^-
FIG. 73. — Transverse section through uterus of rat after ovarian trans-
plantation. The uterus is normal. (See text and cf. Figs. 71 and 72.
From Marshall and Jolly.)
These experiments clearly indicate that the nature of the
ovarian influence is chemical rather than nervous, since the suc-
cessfully grafted ovaries, while still maintaining their functions,
326 THE PHYSIOLOGY OF REPRODUCTION
had lost their normal nervous connections. It is probable,
therefore, that the uterus depends for its proper nutrition upon
substances secreted by the ovaries.
Further evidence in support of the view that the ovary pro-
duces an internal secretion is provided by the results of ovarian
medication or the administration of preparations of ovarian
substance for medicinal purposes. It is somewhat difficult,
however, to know precisely what value to assign to this practice
about which medical authorities still appear to differ. Brown-
Sequard 1 seems to have been the first to employ ovarian ex-
tracts medicinally. He supposed them to produce similar
effects to those brought about by testicular extracts, but they
did not appear to be so powerful. Since Brown-Sequard's time
ovarian preparations have been used medicinally in a large
number of cases with more or less successful results. The fresh
ovaries are themselves taken, or ovarian tissue is given in the
form of fluid or powder (ovarine, oophorine, ovigenine, &c.).
The fresh ovaries or ovarian powder are eaten, but the fluid can
be administered either by the mouth, by the rectum, or by
hypodermic injection. These methods of treatment are said
to have met with considerable success in cases of amenorrhcea,
chlorosis, and menopause troubles, both natural and post-
operative. Some physicians, however, report only a very
moderate or doubtful success, while a few state that the results
are nearly always unsatisfactory.2 The method of administering
the extract by the mouth is open to the criticism that the " active
principle " of the ovarian secretion may be altered in the meta-
bolic processes of digestion. Moreover, it is by no means certain
that the " active principle " may not be destroyed in the manu-
facture of the preparations. Again, it is not unlikely that the
effects of ovarian medication may depend, not only upon the
method of preparing the extracts, but also upon the condition
of the ovaries from which the extracts are made, and it would
seem unreasonable to expect to obtain uniform results from
the indiscriminate usage of ovaries in different stages of cyclical
1 Brown- Sequard, " Des Effets produits chez 1'Homme par des Injec-
tions," &c., C. R. de la Soc. de Biol., 1889.
2 For references to the literature of ovarian medication, see Andrews,
" Internal Secretion of the Ovary," Jour, of Obstet. and Gyn., vol. v., 1904.
ORGANS OF INTERNAL SECRETION
327
activity (e.g. ovaries with prominent follicles like those from
animals " on heat/' or ovaries with corpora lutea like those of
flj-
FIG. 74. — Section through rat's kidney, into the tissue of which an ovary
had been transplanted. (From Marshall and Jolly, Quart. Jour, of
Experimental Physiology.)
ar, artery; c.l., corpus luteum ; g.f. , Graafian follicle; gl., glomerulus of
kidney; ov.st., ovarian strorna ; r.t., renal tubule; z.~.£., zone of
granulation tissue between ovarian tissue and tissue of kidney.
328 THE PHYSIOLOGY OF REPRODUCTION
pregnant animals, or ovaries in a state of relative quiescence
like those of anoestrous animals).
The effects of ovarian medication are discussed at some
length in a memoir by Bestion de Camboulas,1 who describes a
large number of experiments upon dogs, rabbits, and guinea-
pigs, as well as a series of clinical observations. Experiments
were performed on male animals as well as on female ones. The
lethal injection of ovarian extract was found to be about twice
as much in non-pregnant females as in males or pregnant females.
With non-toxic doses the females gained weight, but the males
lost weight. The lesions discovered after lethal doses were
congestion of the viscera, and minute haemorrhages in the
dorsal and lumbar regions of the spinal cord. Bestion also
administered ovarian extract to his patients, and states that
he obtained distinctly beneficial results. Menopause troubles
are described as either disappearing altogether or becoming
much ameliorated, while rapid improvement was observed in
cases of chlorosis and amenorrhcea. Bestion says that ovarian
extract should never be administered to pregnant women,
since it causes such grave results when given to pregnant animals.
Jentzner and Beuttner 2 found that the subcutaneous in-
jection of ovarian extract in castrated animals did not supply
the place of living ovarian substance, and Mr. Carmichael and
the present writer 3 experienced a similar result after making a
series of intra-peritoneal injections of commercial extract,
the uterine atrophy which followed ovariotomy being in no
degree diminished.
It has been shown that the ovary possesses considerable
capacity for regenerating tissue after partial removal, and also
that if one ovary is extirpated the remaining one may undergo
an apparent increase in size, which is probably of the nature of
a compensatory hypertrophy. These facts may perhaps be re-
garded as supplying some further evidence that the ovary is an
organ of internal secretion 4 (cf. the testis, p. 314).
1 Bestion de Camboulas, " Le Sue Ovarien," Paris, 1898.
2 Jentzner and Beuttner, " Experimentelle Untersuchungen zur Frage der
Castratinsatrophie," Zeitschr. /. Geburtsh. u. Gynak., vol. xlii., 1900.
3 Carmichael and Marshall, loc. cit.
4 Carmichael and Marshall, " On the Occurrence of Compensatory Hyper-
trophy in the Ovary," Jour, of Phys., vol. xxxvi., 1908.
ORGANS OF INTERNAL SECRETION 329
According to Loisel,1 the ovary fulfils a purifying function in
the organism, absorbing injurious products which are excreted
with the ova or absorbed as internal secretions. This theory
seems to have little experimental basis at present.
THE FACTORS WHICH DETERMINE THE OCCURRENCE
OF HEAT AND MENSTRUATION
Pflliger 2 advanced the theory that menstruation is brought
about by a nervous reflex, owing its origin to the pressure of the
growing Graafian follicles upon the nerve endings in the ovary.
This view received some support from Strassmann,3 who claimed
to have induced " heat " in animals by injecting gelatine into
their ovaries, and so producing intra-ovarian pressure.
Elizabeth Winterhalter's 4 alleged discovery of a sympathetic
ganglion in the ovary also tended to support this theory ; but
Von Herff 5 discredited her description, which, so far, has re-
ceived no confirmation.
Goltz 6 showed that heat in animals is not brought about
by a cerebral or spinal reflex. In one experiment the spinal
cord of a bitch was transected in the lumbar region ; normal
procestrum, followed by oestrus and conception, occurred as
usual, but copulation was unaccompanied by sensation, though
the animal showed a marked inclination towards the dog.
In another experiment the lumbar part of the spinal cord
was completely removed without interfering with the cyclical
1 Loisel, "Les Poisons des Glandes genitales," C. R. de la Soc. de BioL,
vol. lv., 1903 ; vol. Ivi., 1904 ; and vol. Ivii., 1904.
2 Pfl tiger, tfbcr die Bedtutung und Ursache der Menstruation, Berlin'
1865.
3 Strassmann, Lekrbuch der gerichtlichen Medizin, 1895.
4 Winterhalter, " Bin Sympathisches Ganglion im Menschlichen Ovarium',,
Arch.f. Gyndk., vol. li., 1896.
5 Von Herff, " Giebt es ein Sympathisches Ganglion im Menschlichen
Ovarium," Arch.f. Gynak., vol. li., 1896. For information upon the innerva-
tion of the ovary, see Von Herff, " Uber den feineren Verlauf der Nerven
im Eierstock," Zeitschr. f. Geb. u. Gyncik., vol. xxiv., 1893.
6 Goltz, " Ueber den Einfluss des Nervensystems auf die Vorgange
wahrend der Schwangerschaft und des Gebarakts," Pfliiger's Archiv,vo\. ix.,
1874. Goltz and Ewald, " Der Hand mit verkiirztem Kiickenmark," Pfluger's
Archiv, vol. Ixiil., 1896.
330 THE PHYSIOLOGY OF REPRODUCTION
recurrence of prooestrum and oestrus. Moreover, Sherrington,1
after transecting the spinal cord of a bitch in the cervical region,
and headwards of the connection between the sympathetic
system and the cord, observed that heat of normal duration
and character continued to recur in the animal so operated
upon. The case, described by Brachet,2 of a woman suffering
from paraplegia in the lower part of the body and legs, but who
conceived and became pregnant, may also be cited.
There are other facts which indicate that menstruation is
not caused by a nervous reflex set up by ovulation or by the
pressure of the growing follicles. Gynaecologists have pointed
out that in the human subject ovulation and menstruation are
not necessarily associated, and Heape 3 has shown that the
ovaries of menstruating monkeys do not always contain follicles
in a state approaching ripeness.
But whereas the evidence is clear that heat and menstruation
are not brought about by nervous reflexes arising from the
ovary, it is equally obvious that these processes are dependent
upon some ovarian influence. For, if the ovaries are removed,
heat and menstruation no longer take place.
Some authors, however, have denied this, and cases have
been cited of the occurrence of menstruation after surgical
ovariotomy. For example, three cases have recently been
described by Doran,4 in each of which the two ovaries were
believed to have been removed, although menstruation recurred
at irregular intervals after the operation. Further cases have
lately been reported by Blair Bell 5 and other writers. It seems
probable that these exceptional cases are to be explained on
the supposition that the extirpation of ovarian substance was not
quite complete, and that the tissue which remained behind
underwent hypertrophy subsequently to the operation. That
1 Sherrington, The Integrative Action of the Nervous System, London,
1906.
2 Brachet, Recherches, 2nd Edition, Paris, 1837.
3 Heape, " The Menstruation and Ovulation of Macacus rhesus," Phil.
Trans. B., vol." clxxxviii., 1897.
4 Doran, "Sub-total Hysterectomy for Fibroids," Lancet, Part II.,
November, 1905.
5 Blair Bell, " Preliminary Note on a New Theory of Female Generative
Activity," Liverpool Medico -Chirurgical Journal, July 1906.
ORGANS OF INTERNAL SECRETION 331
this is the true interpretation is rendered the more probable in
view of the cases referred to by Gordon,1 Doran,2 Meredith,3
and others, in which pregnancy occurred after the supposed
removal of both ovaries (see also, p. 343). Doran 4 also records
a large series of cases in which menstruation entirely ceased
after ovariotomy.5
Morris 6 gives an account of a woman aged twenty, who
suffered from amenorrhoea, her uterus being infantile. He
states that he transplanted on to her fundus uteri an ovary
which he obtained from another woman, aged thirty. The
transplantation is said to have been successful, inducing men-
truation after two months. In another case Morris 7 states
that he transplanted an ovary into a woman whose own ovaries
had been previously removed, and that the graft was so far
successful that conception, followed by a normal pregnancy,
occurred as a result. It has been suggested, however, that in
this case a portion of the woman's original ovary may have
been left behind, and that this accounted for the pregnancy
(cf. p. 343). Glass 8 describes a case of a patient who was suffer-
ing from menopause troubles due to the extirpation of the
ovaries. After the transplantation of an ovary from another
woman had been effected, the patient was gradually restored to
health and menstruation was renewed. Dudley 9 mentions a
case in which a double pyosalpinx was removed, and the right
1 Gordon, " Two Pregnancies following the Eemoval of Both Tubes and
Ovaries," Trans. Amer. Gyncec. Soc., vol. xxi., 1896.
2 Doran, "Pregnancy after the Removal of Both Ovaries," Jo ur. Obstet.
and Gyncec., vol. ii., 1902.
3 Meredith, "Pregnancy after Removal of Both Ovaries," Brit. Med.
Jour., Part I., 1904.
4 Doran, "Sub-total Hysterectomy for Fibroids," Lancet, Part II., Nov.
1905.
5 The continuance of menstruation after the removal of two ovaries may
be due to the presence of accessory ovaries which are occasionally known
to exist.
6 Morris, " The Ovarian Graft," New York Med. Jour., 1895.
7 Morris, " A Case of Heteroplastic Ovarian Grafting followed by
Pregnancy," &c., New York Med. Jour., vol. Ixix., 1906.
8 Glass, "An Experiment in Transplantation of the Entire Human
Ovary," Medical News, 1899.
9 Dudley, " tJber Intra-uterine Implantation des Ovariums," Internat. Gyn.
Congress, Amsterdam, 1899.
332 THE PHYSIOLOGY OF REPRODUCTION
ovary implanted on the fundus uteri. The patient menstruated
regularly afterwards. Again, in a case recorded by Cramer of
Bonn,1 the ovary of a woman suffering from osteomalacia was
extirpated and transplanted into a second woman whose genital
organs were much atrophied. As a result of the graft the
genital organs of the woman in whom the ovary was trans-
planted became normal, menstruation started once more, and
the breasts secreted colostrum. In none of these cases, how-
ever, is there any record of post-mortem evidence showing that
the transplanted ovaries had become successfully attached.
Halban 2 states that he found in monkeys that, whereas
menstruation ceased after double ovariotomy, it recurred again
after ovarian transplantation, even though the ovary was
grafted in a position different from the normal one.
Those cases already referred to, in which atrophy of the
uterus took place after the removal of the ovaries, also indicate
the dependence of the menstrual and prooestrous functions
upon the presence of ovarian tissue, since normal heat could not
occur if the uterus were in a condition of fibrotic degeneration,
while certain of Knauer Js experiments 3 afford evidence that
heat can be experienced by animals in which the ovaries are
transplanted to abnormal positions.
Veterinarians are generally agreed that heat does not .occur
in dogs whose ovaries have been extirpated. Moreover,
ovariotomy is sometimes practised on mares in order to prevent
oestrus, and so suppress the vicious symptoms which are liable
to render the animals periodically unworkable.4
Dr. Jolly and the author 5 have shown, further, that normal
procestrum, followed by oestrus, can occur in dogs which only
possess transplanted ovaries, thus confirming the observations
of Knauer and Halban. In the experiments in question the
animals' own ovaries were removed, and a few weeks later the
1 Cramer (H.), " Transplantation rnenschlicher Ovarien," Milnchen. med.
Wochenschr., 1906.
2 Halban, " Uber den Einfluss der Ovarien auf die Entwickelung des
Genitales," Sitz.-Ber. Akad. Wissenschaft, Wien, vol. ex., 1901.
3 Knauer, loc. cit.
4 Hobday, " Ovariotomy of Troublesome Mares," Veterinary Jour., New
Series, vol. xiii., April 1906.
5 Marshall and Jolly, " Contributions to the Physiology of Mammalian
Reproduction: Part II. The Ovary as an Organ of Internal Secretion," Phil.
Trans., B., vol. cxcviii., 1905.
ORGANS OF INTERNAL SECRETION 333
ovaries obtained from other dogs were grafted in abnormal
positions (e.g. between the abdominal muscular layers or on
the ventral border of the peritoneal cavity). The grafts seem
to have become attached, and to have survived for a sufficiently
long period to exercise an influence over the generative system"!"
but they eventually underwent considerable fibrous degenera-
tion, as the post-mortem evidence afterwards showed.
As a result of these experiments it may probably be con-
cluded that the enhanced activity which the ovaries exhibit
during the final stages of follicular development is accompanied
by metabolic changes which result in an increase in the pro-
duction of the ovarian secretion, and that this phenomenon is
the main factor in the periodic recurrence of heat and menstrua-
tion.1 It has been observed that, not only are the internal
and external generative organs affected at these periods, but
there is also a distinct hypertrophy of the breasts, and this,
as Miss Lane-Claypon and Starling 2 have pointed out, is pro-
bably due also to an increase in the ovarian metabolism.3
There is a certain amount of direct evidence that heat and
menstruation are brought about by an internal secretion
elaborated by the ovaries. It has been found that the injection
of fresh ovarian extract obtained from animals which are " on
heat " may produce in ancestrous animals a transient congestion
of the external generative organs resembling that of the normal
prooestrous condition.4 Miss Lane-Claypon and Starling also
1 As already pointed out, menstruation and ovulation are not necessarily
associated. It is probable, however, that the ovarian metabolism is increased
at the menstrual periods, although there may not always be any follicles
present in a sufficiently mature condition to admit of ovulation occurring
in the oestrous periods which normally follow them.
2 Lane-Claypon and Starling, " An Experimental Inquiry into the Factors
which Determine the Growth and Activity of the Mammary Glands," Proc.
Roy. Soc., B., vol. Ixxvii., 1906.
3 According to Pearl and Surface ("The Nature of the Stimulus which
causes a Shell to be formed on a Bird's Egg," Science, New Series, vol. xxix.,
1909), the stimulus which excites the activity of the shell-secreting glands
in the fowl's oviduct is mechanical, being brought about by a strictly local
reflex. The shape of the egg is determined by the muscular activity of the
cells of the oviduct (Pearl, " Studies on the Physiology of Keproduction
in the Domestic Fowl : I. Regulation in the Morphogenetic Activity of the
Oviduct," Jour, of Exp. Zool., vol. vi., 1909).
4 Marshall and Jolly, loc. cit.
334 THE PHYSIOLOGY OF REPRODUCTION
have described congestion in the uterus after the injection of
ovarian extract ; but, in their experiments, the ovaries employed
were those of pregnant animals.
Further evidence that the prooestrous and cestrous conditions
are produced by substances circulating in the blood, but not
necessarily elaborated in the ovaries, is supplied by certain facts
recorded by Halban.1 This author affirms that the milk of
suckling sows is affected during the periods of heat, in conse-
quence of which the young are liable to develop unhealthy
symptoms." In a similar way the milk of women is said to
be affected during menstruation. Moreover, according to
Youatt,2 cows can be brought " on heat " artificially by feeding
them on milk supplied from other cows which are in that con-
dition.
Heape 3 has suggested that heat may be due to a " generative
ferment " which he supposes to be periodically present in the
blood. At the same time he is of opinion that a hypothetical
substance called " gonadin," which is secreted by the generative
glands, is also an essential factor. The precise relation in
which gonadin and the generative ferment are supposed to
stand to one another is not at present clear, but there is no in-
consistency between a belief in their existence and the views
which are adopted here.
Assuming that heat and menstruation are brought about,
either directly or indirectly, through a stimulus depending upon
the secretory activity of the ovary, it is still an open question
as to what part of the organ is concerned in the process.
Fraenkel 4 has supposed that the secretion in question is supplied
by the corpus luteum. This conclusion is based upon nine
cases in which the corpus luteum was destroyed by the cautery,
and in eight of which the next menstrual period was missed. In
the remaining case it is supposed that the secretion responsible
for producing menstruation had already been formed in sufficient
quantity and passed into the circulation at the time of the
cauterisation. FraenkeFs theory, however, is disproved by the
1 Halban, loc. cit. 2 Youatt, Cattle, London, 1835.
3 Heape, " Ovulation and Degeneration of Ova in the Rabbit," Proc. Roy.
Soc., B., vol. Ixxvi., 1905.
4 Fraenkel, "Die Function des Corpus Luteum," Arch. /. Gyndk.,
vol. Ixviii., 1903.
ORGANS OF INTERNAL SECRETION 335
fact that ovulation in most Mammals does not occur until oestrus,
or, at any rate, until the end of the procestrum (see p. 135),
and consequently corpora lutea are not present in the ovaries
(for the corpora lutea dating from one oestrus do not always
persist until the next oestrus, which may be many months after~
wards). Heape's observations 1 on the absence of corpora
lutea in menstruating monkeys may be again cited in this con-
nection. Moreover, Ries 2 has reported a case of a woman
with whom menstruation occurred normally after an operation in
which an oozing corpus luteum, which was a source of haemorrhage
in the peritoneal cavity, had been peeled out. It should be
mentioned that Fraenkel's views on menstruation are part of a
general theory which is discussed more fully below (p. 338).
Seeing that the corpus luteum is not responsible for inducing
menstruation, it becomes necessary to conclude that either the
follicular epithelial cells or the interstitial cells of the ovarian
stroma (or both of these) are concerned in bringing about the
process (see p. 124).
It has already been shown that the breeding season, and
consequently the recurrence of the cestrous cycle, are controlled
to a great extent by the general environmental conditions,
since these affect the physical state of the body (Chapters I.
and II.). This is particularly well seen in certain of the domestic
animals, in which " heat " may be caused to recur more fre-
quently by the supply of special kinds of stimulating foods
(p. 599). It would appear, therefore, that the metabolic activity
of the ovaries is increased by these methods, and that the prob-
lematical internal secretion is elaborated in greater quantity.
Lastly, it must not be forgotten that, whereas it is exceedingly
probable that the procestrous changes of the uterus are brought
about by a specific excitant or hormone 3 arising in the ovaries,
1 Heape, " The Menstruation and Ovulation of Macacus rhesus" Phil.
Trans., B., clxxxviii., 1897.
2 Hies, " A. Contribution to the Function of the Corpus Luteum," Amer.
Jour. Obstet., vol. xlix., 1904.
3 Starling has proposed the term hormone (from the Greek, 6p/j.aw, I excite
or arouse) for such internal secretions or excitants of a chemical nature.
Thus, secretin, or the internal secretion of the duodenum, which excites
pancreatic secretion, is a hormone. See Starling, " The Chemical Cor-
relation of the Functions of the Body," Croonian Lectures, London, 1905 ;
also Lane-Claypon and Starling, loc. cit.
336 THE PHYSIOLOGY OF REPRODUCTION
little or nothing is known concerning the source of that dis-
turbed state of the nervous metabolism, the existence of which
during oestrus is so plainly manifested in the display of sexual
feeling.
THE FUNCTION OP THE CORPUS LUTEUM
Various theories have been put forward to explain the
formation and presence of the corpus luteum. According to
one view, which is still sometimes taught, the development of
this structure is merely a result of the excessive vascularisation
which characterises the entire internal generative tract during
the period of pregnancy. Very little consideration of the actual
facts is needed to convince one of the inadequacy of this ex-
planation. The blood supply to the generative organs is greatest
during the later stages of pregnancy, when the corpus luteum
is becoming diminished in size. Moreover, the rapid hyper-
trophy of the luteal cells takes place independently of pregnancy
during the very early stages of development at a time when
there is no appreciable congestion of the genital organs. Ac-
cording to another theory, the corpus luteum is of the nature
of a stop-gap, whose purpose is to preserve the cortical circula-
tion of the ovary by preventing an excessive formation of
scar-tissue.1
Prenant 2 seems to have been the first to suggest that the
corpus luteum was a ductless gland. He supposed it to produce
an internal secretion which exercised an influence over the
general metabolism in the manner attributed to the internal
ovarian secretion. The phenomenon of chlorosis was explained
as being due to the absence of this secretion. Prenant supposed
also that the corpus luteum had the further function of pre-
venting ovulation during pregnancy or between the oestrous
periods.
This theory was supported by Regaud and Policard,3 who
1 Clark, " Ursprung, Wachstum, und Ende des Corpus Luteum," Arch,
f. Anat. u. Phys., Anat. Abth., 1898. Whitridge Williams, Obstetrics, New
York, 1903.
2 Prenant, "La Valeur Morphologique du Corps Jaune," Rev. Gen. des
Sciences, 1898.
3 Regaud and Policard, " Fonction Glandulaire de 1'Epithelium Ovarique
chez la Chienne," C. R. de Soc. de Biol., vol. liii., 1901.
ORGANS OF INTERNAL SECRETION 337
stated that, by means of special methods of staining, droplets
of a secretory substance could be detected in the cells of the
corpus luteum of the hedgehog.
Beard l independently suggested that the corpus luteum is
a contrivance to suppress ovulation during pregnancy, white^
he supposed it to degenerate before parturition in order to
admit of ovulation occurring immediately afterwards. It must
be pointed out, however, that in many Mammals, if not in the
majority, the breeding season does not recur until after an
anoestrous period, which is often of considerable duration, and
that it is extremely improbable that ovulation occurs during
this period.
Beard's theory has been adopted by Sandes.2 who investi-
gated the corpus luteum of the marsupial cat (Dasyurus viver-
rlnus, see p. 149). This author states that in Dasyurus, as in
most other Mammals, the corpus luteum disappears towards
the end of the lactation period, when the next oestrus is ap-
proaching, and the follicles are beginning to grow in preparation
for the ensuing ovulation. He says, further, that as soon as
the corpus luteum is formed, the ova in the surrounding follicles,
which were up to that time in various stages of active de-
velopment, begin to undergo atrophy. This atrophy com-
mences in the follicles in closest proximity to the newly formed
corpus luteum, and is continued in the surrounding follicles in
ever-widening circles. Sandes suggests that this result is
brought about by mechanical pressure, or is due to the internal
secretion of the corpus luteum, if it has one. Without in any
way disputing the accuracy of the facts which Sandes describes,
it is difficult to understand what advantage is gained by a
mechanism having a not more important object than that of
securing the degeneration of the surplus ova within the ovary
instead of externally to it, and it is not easy to see how, ac-
cording to the usually accepted doctrines of utility and natural
selection, an organ having such a purposeless function could
ever have been developed at all.
Gustav Born was the first to suggest that the function of
1 Beard, The Span of Gestation and the Cause of Birth, Jena, 1897.
2 Sandes, " The Corpus Luteum of Dasyurus viverrinus," Proc. Linnean
Soc., New South Wales, vol. xxviii., 1903.
Y
338 THE PHYSIOLOGY OF REPRODUCTION
the corpus luteum might be to provide an internal secretion
which assisted in the attachment of the embryo to the uterine
mucosa. Unable to undertake the investigation himself, he
persuaded Ludwig Fraenkel to put his theory to an experi-
mental test. For this purpose a series of experiments upon
rabbits was proceeded with, the ovaries being removed at
intervals varying from one to six days after the occurrence
of coition, the period of gestation in this animal being thirty
days. The rabbits were afterwards killed, when it was found
that the extirpation of the ovaries had prevented the fixation of
the embryos, or had caused these to be aborted. In other cases
the corpora lutea are described as having been burnt out by
the electric cautery without destroying the rest of the ovaries,
and these experiments led to a similar result. Control experi-
ments were performed by removing one ovary while leaving
the other, and by destroying some of the corpora lutea but not
all, and in the majority of these cases the animals produced
young. The experiments resulted, therefore, in supporting the
view that there is an intimate connection between the presence
of the corpus luteum and the occurrence of pregnancy, and that
this connection is in a certain sense one of cause and effect.
Apart from the experimental evidence, Fraenkel adduces
certain other facts which tend to support the theory that the
corpus luteum is an organ of internal secretion. He points
out that its general structure is eminently suggestive of its
being a ductless gland, since it is formed mainly of large
epitheloid cells surrounded by a network of capillaries and
arranged in regular rows or columns not unlike those of the
cortex of the supra-renal body. Moreover, the increase in the
size of the corpus luteum, until it becomes larger than a Graafian
follicle, seems inexplicable on any other view. This unusual
capacity for growth is clearly out of all proportion to that of
the rest of the ovary, and it is pointed out, further, that when
the corpus luteum is most hypersemic, the other part of the
ovary is unusually anaemic, while towards the end of pregnancy,
when the increase in the blood supply to the generative organs
1 Fraenkel and Cohn, " Experimentelle Untersuchungen iiber den Einfluss
des Corpus Luteum auf die Insertion des Eies," Anat. Anz., vol. xx., 1901 ;
Fraenkel. loc. cit.
ORGANS OF INTERNAL SECRETION 339
is at its height, the corpus luteum is often reduced to little more
than a scar. Fraenkel also lays some stress on the discovery
that the luteal cells are derived from the folhcular epithelium
and not from the connective tissue of the stroma. Furthermore,
he observes that whereas many cases have been recorded ^n
which double ovariotomy was performed during pregnancy
without interfering with the further course of development, in
none of these, so far as he is aware, was the operation conducted
in the early weeks.
Fraenkel observes also that in non-placental Mammals
(Marsupials and Monotremes) the corpus luteum is rudimentary
or does not exist at all. Sandes,1 who has carefully described
the formation of the corpus luteum in the marsupial cat, points
out that this is erroneous, and says that there is a large corpus
luteum in the members of both these groups. It should be
remembered, however, that in Marsupials the embryo is
nourished by a " yolk-sac placenta," while in at least one genus
(Perameles) a definite allantoic placenta exists. In Monotremes
there is a pronounced hypertrophy of the follicular epithelium
following upon ovulation, but the corpus luteum is not normal
in this group, since there appears to be no ingrowth of con-
nective tissue or blood-vessels from the follicular wall (see p. 149).
A similar objection, that might be raised in opposition to
FraenkeFs hypothesis, is that structures resembling corpora
lutea have been found in the ovaries of certain of the lower
Vertebrates (see p. 151). This resemblance relates chiefly to the
hypertrophy of the cells of the follicular epithelium after the
discharge of the ova. Such an objection is not to be regarded
as a serious one, for there is nothing improbable in the sup-
position that rudimentary corpora lutea, providing probably
some sort of secretion, should have been developed before the
acquirement of the function, which, according to Fraenkel's
hypothesis, is possessed by the fully formed structure which
characterises the placental Mammalia.
Fraenkel has also pointed out, as an argument in favour of
his theory, that in ectopic or extra-uterine pregnancy the uterus
undergoes the usual changes although there is no ovum in
the uterine cavity. It is clear, therefore, that the changes do
1 Sandes, loc. cit.
340 THE PHYSIOLOGY OF REPRODUCTION
not occur simply as a consequence of the presence of the
ovum. It is also pointed out that in normal pregnancy the
uterine changes commence before the ovum enters the uterus.
Again, the theory that the corpus luteum is responsible for
the attachment and early development of the embryo receives
some support from those cases in which pathological conditions
in the embryo have been found associated with pathological
conditions in the corpus luteum.1 Thus lutein cysts are
frequently found in apparent correlation with chorionepi-
thehomata.
Fraenkel's general conclusions regarding the functions of
the corpus luteum may be summarised as follows : The corpus
luteum is a ductless gland which is renewed every four weeks
during reproductive life in the human female, and at different
intervals in the various lower Mammals. Strictly speaking,
there is only one corpus luteum which represents the ovarian
organ of internal secretion, and is regenerated periodically in
slightly different positions in the ovaries. Its function is to
control the nutrition of the uterus from puberty until the meno-
pause, to prevent it from lapsing into the infantile condition or
undergoing atrophy, and to prepare its mucous membrane
for the maintenance of the ovum. If the ovum be fertilised,
the corpus luteum is responsible for maintaining the raised
nutrition of the uterus during the first part of gestation. If
the ovum be unfertilised it merely produces the hyperasmia of
menstruation, and then undergoes degeneration until it is
renewed in a fresh position. Since the corpus luteum is, par
excellence, the ovarian gland, " lutein " or the extract of this
organ, and not preparations of the entire ovary, should be
employed for the purposes of ovarian medication.
Reasons have already been given for concluding that this
extended theory of the meaning and function of the corpus
luteum is untenable (p. 334). The fact that in a very large
number of animals, heat, and presumably, therefore, ovulation,
occur at infrequent intervals does not support it, while it has
been shown that, in some animals at any rate, ovulation does
1 Cf. Malcolm Campbell, " Pathological Condition of the Ovaries as a
Possible Factor in the Etiology of Uterine Fibroids," Scottish Med. and Surg.
Jour., vol. xvi., 1905.
ORGANS OF INTERNAL SECRETION 341
not take place until oestrus, and consequently that at the
time of the prooestrous hypersemia there are no corpora lutea
present in the ovary. These facts, however, are in no way
opposed to that part of FraenkeFs theory which assigns to the
corpus luteum the function of governing the fixation of the
ovum and helping to maintain its nutrition during the first
stages of pregnancy.
Dr. Jolly and the author l have carried out a series of experi-
ments upon dogs and rats in which the ovaries were extir-
pated at different stages during pregnancy, as in FraenkeFs
experiments upon rabbits. In the experiments on dogs,
ovariotomy was performed at intervals ranging from three days
to four weeks after impregnation. The pregnancy was dis-
continued in every case excepting one, in which a portion of the
right ovary which contained the degenerate remains of two
undoubted corpora lutea were found post mortem, three days
after parturition, when the dog was killed, In this experiment
ovariotomy was performed three days after copulation, and
parturition occurred fifty days subsequently. Only a single
pup was produced, and birth was premature. The pup died
after being suckled normally for three days. The ovaries were
also removed from a large number of rats, most of which were in
early stages of pregnancy. Pregnancy was continued in no
case in which ovariotomy was performed during the first six
days. In other cases, in which the ovaries were removed at
periods varying from the sixth day until near the end of
pregnancy, the young were produced normally at full time.2
Control experiments were also carried out in which the ab-
dominal cavity was opened up during an early stage of pregnancy
* and the ovaries were cauterised, or in which one ovary was re-
moved and not the other, and in these experiments the course
of pregnancy was not interfered with.3 We purposely refrained
from attempting to extirpate the corpora lutea only while
leaving the rest of the ovary, as it appeared to us to be
practically impossible to destroy the whole of the luteal tissue
1 Marshall and Jolly, loc. cit.
2 In our paper the period of gestation in the rat was wrongly computed
at twenty-eight days. It is in reality about twenty-one days.
3 Cf. Carmichael and Marshall, loc. cit.
THE PHYSIOLOGY OF REPRODUCTION
without injuring the entire organ. The ovaries during pregnancy
consist very largely of corpora lutea, and any attempt in a
relatively small animal to discriminate between luteal tissue
and stroma, while the ovary was lying in its normal position in
the body cavity, seemed in our judgment to be impracticable.
It will be seen that our experiments on the results of ovari-
otomy during pregnancy fully confirm those of Fraenkel. It
must be pointed out, however, that there is no evidence that the
corpus luteum governs the fixation of the embryo in any other
than the indirect sense implied in the supposition that the
secretion elaborated by that organ acts as a stimulus which excites
the uterine mucosa to undergo the necessary hypertrophy.
In this general sense, also, it is probably true that the luteal
secretion (or, at any rate, the secretion of the ovary) assists in
nourishing the embryo during the first stages of pregnancy,
since there is every reason for concluding that it helps to
maintain the raised nutrition of the uterus. It has been shown
that the presence of the ovaries is not essential for the con-
tinuance of pregnancy in the later stages, when the corpora
lutea are in process of degeneration. It would seem not un-
likely, therefore, that the atrophic changes (fibrosis) which
take place in the decidua serotina, or maternal placenta, in the
later part of the gestation period are directly correlated with the
degeneration of the corpus luteum.1
Cases have been recorded by Essen-Moller,2 Graefe,3 and
Flatau,4 in which pregnancy was not interrupted by double
ovariotomy in women when performed in the early stages of
pregnancy. These cases are undoubtedly very exceptional,
and it seems legitimate to conclude that a small portion of an
ovary, probably containing luteal tissue, was left behind acci- '
1 It has been suggested that the corpus luteum contributes an essential
factor in the nourishment of the embryo through the trophoblast, and that
it consequently ceases to be functional in the later part of pregnancy when
the trophoblast is superseded by the allantoic placenta. See Andrews,
loc. cit.
2 Essen-Moller, " Doppelseitige Ovariotomie im Anfange cler Schwanger-
schaft," Central./. Gyndk , vol. xxviii., 1904.
3 Graefe, "Zur Ovariotomie in der Schwangerschaft," Zeitschr. f. Geb. u.
Gynak., vol. Ivi., 1905.
4 Flatau, " Ueber Ovariotomie wahrend der Schwangerschaft," Arch. /.
Gynak., vol. Ixxxii., 1907.
ORGANS OF INTERNAL SECRETION 343
dentally at the time. of the operation. So able and experienced
an operator as Bland Sutton l has recently testified to the
extraordinary difficulty experienced in removing the whole of
the ovarian tissue in ovariotomy, and the distinguished French
obstetrician, Lucas-Champonniere,2 has expressed himself in the
same sense, so that there is nothing unreasonable in the assump-
tion that the operation of removal is sometimes incomplete
when performed on pregnant women.
Daels 3 has recently recorded a large series of experiments
upon guinea-pigs and rats in which he found that bilateral
castration invariably interrupted the course of pregnancy
during rather more than the first half of its duration. In
control experiments portions of mesentery or other tissue, or
only one ovary instead of both, were extirpated, and in these
cases the pregnancy was continued. Furthermore, Kleinhaus
and Schenk 4 found that destruction of the corpora lutea of
rabbits, after the ninth day of gestation, did not necessarily pro-
duce abortion, but that the same operation at an earlier period
invariably brought the gestation to a premature end.
According to Ancel and Bouin,5 the rabbit's uterus undergoes
growth, vascularisation, and muscular hypertrophy after ovula-
tion even although the ova are not fertilised (e.g. owing to the
vasa deferentia of the male having been cut). These changes
are said to be followed by regression, which sets in after the
thirteenth day. According to Ancel and Bouin, therefore,
there is a close parallelism between the growth and regression of
the corpus luteum and a series of cyclical changes which take
place in the uterus. There is also said to be a parallelism
1 Bland Sutton, " A Clinical Lecture on the Value and Fate of Belated
Ovaries," Medical Press, vol. cxxxv. (July 31) 1907.
2 Lucas-Champonniere, " Sur une Observation de Graffe Ovarienne Suivie
de Grossesse," Jour, de Med. et de Chirurgie Pratiques, vol. Ixxviii. (May)
1907.
3 Daels, " On the Relations between the Ovaries and the Uterus," Surgery
Gynaecology and Obstetrics, vol. vi., 1908.
4 Kleinhaus and Schenk, " Experimentales. zur Frage nach der Funktion
des Corpus Luteum," Zcitsehr. f. Geb. u. Gynalc., vol. Ixi., 1907.
5 Ancel and Bouin, " Sur la Fonction des Corps jaunes," G. R. de la Soc.
de BioL, vol. Ixvi., 1909 ; " Le Developpement de la Glande Mammaire
pendant la Gestation est determine; par le Corps jaune," C. R, de la SQC. de
Biol., vol. Ixvii., 1909.
344 THE PHYSIOLOGY OF REPRODUCTION
between the development of the corpus luteum and the growth
of the mammary gland in the rabbit.1
Dubreuil and Regaud,2 however, as a result of further ex-
periments, are very doubtful whether the corpus luteum has any
influence over the non-gravid uterus. On the other hand, the
observations of Niskoubina 3 tend to confirm those of Ancel and
Bouin.
According to Loeb,4 deciduomata (i.e., nodules having the
structure of decidua) can be produced experimentally in the
uterine mucosa of the guinea-pig by making a number of trans-
verse and longitudinal cuts so as to break the continuity of the
tissue. The nodules originate through a proliferation of the
interglandular connective tissue. Loeb states further that this
can only happen during a certain definite period after the occur-
rence of copulation or heat. The changes cannot be induced on
the first day after heat, nor after the tenth day, but deciduomata
are readily formed between the fourth and eighth days. The
uterus is therefore most responsive when freshly formed corpora
lutea are present in the ovaries. The changes were not excited
by the presence of ova in the uterus, since they took place when
the lower part of that organ was ligatured off so as to prevent
the passage of the ova. On the other hand, if the ovaries were
extirpated deciduomata could not be produced. If the corpora
lutea were as far as possible burnt out of the ovaries by the
electric cautery, deciduomata were not generally produced ; but
owing to the difficulty of properly performing these experiments,
the results were not quite conclusive. Lastly, when pieces of
uterus were transplanted into the subcutaneous tissue, deciduo-
mata were formed in the grafted pieces. It is concluded, there-
fore, that the ovaries at certain periods after ovulation (and
probably the corpora lutea) elaborate a predisposing substance
1 Ancel and Bouin, loc. cit.
2 Dubreuil and Kegaud, " Sur les Relations fonctionelles des Corps jaunes
avec 1'Uterus non gravide," I. II. III. and IV., C. R. de la Soc. de Biol., vol.
Ixvii., 1909. See also earlier papers in vol. Ixv., 1908, and vol. Ixvi., 1909.
3 Niskoubina, " Recherches experimentales sur la Fonction des Corps
jaunes," (7. R. de la Soc. de Biol, vol. Ixvi., 1909.
4 Loeb (L.), "The Production of Deciduomata, and the Relation between
the Ovaries and the Formation of the Decidua," Jour. Amer. Med. Assoc.,
vol 1. (June 6), 1908. Medical Record, vol. Ixxvii. (June 25), 1910.
ORGANS OF INTERNAL SECRETION 345
in the presence of which indifferent stimuli (traumatisms), may
produce deciduomata.
It has been shown that the uterine mucosa undergoes atrophy
after the complete removal of the ovaries, and it seems hardly
probable that this process can be arrested by the presence oFa
fertilised ovum in the early stages of pregnancy. On the other
hand, it is scarcely conceivable that an ovum could become
attached to a uterine mucous membrane which was in process
of degenerating. It would appear, however, that in the latter
half or two-thirds of pregnancy, when the uterus has already
undergone great hypertrophy, the presence of the ovaries may
be dispensed with.1 Furthermore, it has just been mentioned
that the maternal placenta undergoes a partial degeneration in
the later stages of embryonic development.
Miss Lane-Claypon 2 has shown that the interstitial cells of
the ovarian stroma undergo an increase in size during the period
of gestation, but this increase is not so great as that of the
luteal cells. Consequently, she suggests that these cells also
may produce a secretion of the nature postulated for the cells
of the corpus luteum. If this is so, the circumstance that the
interstitial cells do not hypertrophy to the same extent as the
luteal cells may perhaps be ascribed to the different conditions
of mechanical pressure existing in the ovarian stroma.
THE SUPPOSED INTERNAL SECRETION OF THE UTERUS
Although the bulk of evidence obtained clinically points to
the conclusion that the uterine functions fall into abeyance
after the extirpation of the ovaries, while the relatively few
exceptions to this rule are probably to be explained on the sup-
position of incomplete removal, some surgeons and gynaecologists
have adopted the view that the uterus is capable of functional
activity independently of the ovaries. A few writers have even
gone further, and have affirmed the belief that the ovarian
functions themselves are dependent upon uterine influence.
1 It has yet to be proved, however, that the further course of development
is absolutely normal after ovariotomy in the later part of pregnancy.
2 Lane-Claypon, " On the Origin and Life-History of the Interstitial Cells
of the Ovary of the Rabbit," Proc. Roy. Soc., B., vol. Ixxvii., 1905.
346 THE PHYSIOLOGY OF REPRODUCTION
Zweifel and Abel,1 in describing the after-histories of cases
of hysterectomy, stated that, in their experience, when the
whole of the uterus was removed, entire atrophy of the ovaries
always followed, so that menopause symptoms set in similar
to those occurring after ovariotomy. In those cases, however,
in which a portion of the uterine mucous membrane was con-
served, menstruation continued and there were no menopause
symptoms. Consequently, these surgeons have advocated the
operation of sub-total hysterectomy wherever possible in pre-
ference to complete removal, believing that the functional
activity of the ovary is in some way dependent on the presence
of the uterus.
Doran,2 in tracing the after-histories of sixty cases of sub-
total hysterectomy, is disposed to concur with Zweifel and
Abel in advising that the uterus should be removed above the
cervix. In support of this contention he cites two cases in
which menstruation persisted after the removal of the body of
the uterus, the cervix being left behind.
Mandl and Burger, 3 in a monograph dealing with the sub-
ject, express the belief that in those cases in which the ovaries
are conserved after hysterectomy there is a gradual cessation
of function on the part of these organs, resulting from their
degeneration.
Holzbach,4 on the other hand, states that as a rule the ovaries
do not atrophy after hysterectomy, and that, when such de-
generation does occur, it is probably due to interference with the
nervous connections consequent upon the operation of removal.
Blair Bell 5 has suggested that menstruation is brought about
by an internal secretion of the uterus, while he supposes ovula-
tion to depend on the circulation of this secretion, which he
calls " uterine."
1 Zweifel, " Deutsche Gesellschaft fiir Gynakologie in Berlin," Zentral. f.
Gynak., No. 21, 1899. Abel, " Dauererfolge der Zweifelschen Myomek-
tomie," Arch.f. Gyncik., vol. Ivii., 1899.
2 Doran, "Sub-total Hysterectomy for Fibroids," Lancet, Part II.,
November 1905.
3 Mandl and Burger, Die Biologische Bedeutung der Eierstocke nach
Entfernung der Gebdrmutter, Leipzig, 1904.
4 Holzbach, " Ueber die Function der nach Totalextirpation des Uterus
zurtickgelassen Ovarien," Arch.f. Gyndk., vol. Ixxx., 1906.
5 Blair Bell, loc. tit.
ORGANS OF INTERNAL SECRETION 347
Bond l has put forward the view that the ovarian secretion
is influenced by a saline secretion from the anoestrous uterus,
the two, however, acting antagonistically to one another, so
that the prevention of the uterine secretion by hysterectomy
favours the hypertrophy of the ovaries. Bond's view, therefore,
is diametrically opposed to that of Blair Bell.
Bond records two experiments on the results of hysterectomy
in rabbits. In one the entire uterus was removed and the
animal killed after five months. Both ovaries were found to
be normal. In the other experiment the left uterine cornua
only was extirpated, and the rabbit was killed after five months.
In this case also the ovaries showed no signs of degeneration.
As a result of these experiments Bond affirms that the pre-
vention of the saline secretion of the uterine mucosa by previous
hysterectomy favours the overgrowth of luteal tissue in the ovary.
Stress has been laid by various writers upon the well-known
fact that whereas the corpora lutea of the ovary continue to
grow for a considerable period of time if pregnancy supervenes
after ovulation, this hypertrophy soon ceases in the absence of
pregnancy. Bond records an experiment upon a rabbit in
which one of the ovaries, after transplantation in an abnormal
position, was found to contain a somewhat aberrant " corpus
luteum of pregnancy " in association with a gravid uterus.
Such observations are regarded by him as supplying evidence
of an internal uterine secretion acting on the ovaries and so
exciting a growth of luteal tissue. This secretion is supposed
by Bond to be quite different from the saline fluid elaborated
by the anoestrous uterus.2 It must be remembered, however,
that pregnancy produces a profound influence over the entire
organism, and not merely over the ovaries.
Certain other authors, such as Loewenthal,3 have suggested
theories which imply a dependence on the part of the ovaries
upon some function of the uterus ; but, excepting for the
two experiments of Bond referred to above, and a series of
1 Bond, " Some Points in Uterine and Ovarian Physiology and Pathology
in Babbits," British Med. Jour., Part II., July 1906.
2 Bond, " Certain Undescribed Features in the Secretory Activity of the
Uterus and Fallopian Tubes," Jour. Phys., vol. xxii., 1898.
3 Loewenthal, " Eine neue Deutung des Menstruationprocess," Arch. f.
Gyndk., vol. xxiv., 1884.
348 THE PHYSIOLOGY OF REPRODUCTION
experiments undertaken by the author in collaboration with
Mr. Carmichael,1 no systematic investigation ever appears to
have been attempted upon the effects of hysterectomy.
In our experiments we removed the uterus, either entirely
or leaving only the cervix, from a number of very young
immature rabbits. The animals Were killed after they had
become fully grown — in some cases not until ten months after
the operation. In every experiment the ovaries were found to
have developed normally. In some cases also copulation was
observed on the rabbits being put with the buck. Many of the
ovaries contained typical corpora lutea, showing that ovulation
had taken place. Also in four experiments on fully grown rats
hysterectomy was performed, and the animals were killed several
months subsequently. The ovaries in no instance showed any
indications of atrophy. On the other hand, marked uterine
degeneration was observed in rats after the removal of the
ovaries for shorter periods of time.2
As a result of these experiments, it may be concluded that
the growth and development of the ovaries is in no way de-
pendent upon the presence of the uterus. Such a conclusion is
no doubt opposed by some of the clinical evidence, but it is
one which was to be expected on phylogenetic grounds, since the
uterus is an organ which came into existence comparatively
recently in the course of vertebrate evolution, whereas the
ovary is common to all Metazoa. It is possible, in those surgical
cases in which the ovaries underwent atrophy after the removal
of the uterus, that this was due to vascular interference.3
1 Carmichael and Marshall, Proc. Roy. Soc., loc. cit.
2 Marshall and Jolly, "Results of Removal and Transplantation of
Ovaries," Trans. Roy. Soc. Edin., vol. xlv., 1907.
3 Boston has recorded four cases of women where the uterus was con-
genitally absent, but in whom the development of the breasts and other
changes relating to puberty excepting menstruation were experienced.
Sentiment, sexual desire, and sexual sensation are stated to have been normal
in each case ("Absence of the Uterus in Three Sisters and Two Cousins,"
Lancet, Part I., Jan. 1907). It may also be mentioned that Sellheim found
that removal of the oviducts in pheasants does not result in a shrivelling
up of the ovaries and the assumption of secondary male characters as has
been stated (Zeit. f. Gynak., 1904, No. 24). It has not been determined
whether the generative organs (apart from the uterus) undergo the character-
istic prooestrous changes after hysterectomy, since these changes are com-
paratively slight and difficult to detect in rabbits.
ORGANS OF INTERNAL SECRETION 349
THE CORRELATION BETWEEN THE GENERATIVE ORGANS
AND THE DUCTLESS GLANDS
Noel Paton 1 and Henderson 2 have shown that there _
is a reciprocal relation between the thymus and the testis,
each checking the growth of the other. This conclusion is
based on a series of observations on cattle and guinea-pigs. In
the former it was found that castration delayed the onset of
the atrophy of the thymus, for the average weight of that organ
in bulls up to three and a quarter years old was considerably less
than that in oxen. In guinea-pigs Paton found that, in those
animals in which the thymus was removed at a time prior to
the normal period of atrophy for that organ, there was an in-
crease in the growth of the testis. On the other hand, Soli 3 states
that extirpation of the thymus, carried out in young rabbits,
guinea-pigs, and fowls, caused inhibition of testicular development,
and sometimes even complete arrest of growth by that organ.
Fichera 4 observed a constant hypertrophy of the pituitary
body (hypophysis) in capons, oxen, buffaloes, and rabbits, cas-
trated in early life — that is to say, an increase in weight by that
organ as compared with the pituitary glands of other animals
of the same kind, weight, and age. The increase in weight was
associated with a rich blood supply, and an increase in the number
of eosinophyl cells. These observations are confirmed for young
dogs by Cimorini,5 who states that the changes in the pituitary
were similar to those occurring after removal of the thyroids.
According to Pepere,6 there is probably no specific hypertrophy
of the hypophysis in relation to the extirpation of any particular
1 Paton, "The Relationship of the Thymus to the Sexual Organs," Jour,
of Phys., vol. xxxii., 1904.
2 Henderson, "On the Relationship of the Thymus to the Sexual
Organs," Jour, of Phys., vol. xxxi., 1904.
3 Soli, "Contribution h, la Connaissance de la Formation du Thymus chez
le Poulet et chez quelques Mammiferes," Arch. Ital. de BioL, vol. Ixii., 1909.
4 Fichera, " Sulla ipertrofta della glandula Pituitaria consecutiva cas-
trazione," Policlinico, vol. xii., 1905.
5 Cimorini, " Sur 1'Hypertrophie de 1'Hypophyse cere*brale chez les
Animaux thyre"oidectomise"s," Arch. Ital. de BioL, vol. xlviii., 1907.
6 Pepere, " Sur les Modifications de Structure du Tissu Parathyroidien
normal et accessoire (thymique) en rapport avec sa Fonction vicariante,"
Arch, de Med. Exper., vol. xx., 1908.
350 THE PHYSIOLOGY OF REPRODUCTION
ductless gland in the organism, but that the reaction of the
cellular elements, though varying in response to different con-
ditions, shows also many characters referable to a common cause.
It has been shown further that in cases of giantism and
acromegaly, in which the pituitary body is enlarged, the sexual
organs may be very imperfectly formed.1 Thus, the uterus
is often infantile, the ovaries are rudimentary, or the penis is
ill-developed. (See also final footnote, p. 356.)
It is well known that there is a correlation between the
sexual organs and the thyroids. These glands undergo enlarge-
ment during menstruation and pregnancy in women, and Freund 2
has shown that similar changes occur during the heat periods of
many of the lower mammals. He has pointed out further, that
swelling of the thyroid, at the time of puberty, often leads to
goitre, and that this disease commonly begins at a period of
menstruation. These facts are cited by Gaskell 3 as evidence
of a special connection between the thyroid and the sexual organs
— the former being held to represent the uterus of the scorpion,
Alquier and Thauveny 4 state that after the partial or complete
removal of the thyroids and parathyroids menstruation and
conception are very infrequent, but this result may be due to
the general metabolic disturbance arising from the absence of
the glands.
There is some evidence of a correlation existing between the
sexual organs and the supra-renals. Thus Gottschau 5 states
that in rabbits, changes occur in these organs during pregnancy,
the outer zone of the cortex becoming twice its normal thickness,
whereas the medulla is said to become thinner. Similarly,
Stilling 6 states that in frogs during the pairing time, the medulla
1 Woods Hutchinson, " The Pituitary Gland as a Factor in Acromegaly
and Giantism," New York Med. Jour., 1900.
2 Freund, " Die Beziehungen der Schilddriise zu den weiblichen Ge-
schlechtsorganen," Deutsche Zeitsch. f. Chir., vol. xviii., 1883.
3 Gaskell, The Origin of Vertebrates, London, 1908.
4 Alquier and Thauveny, "Etat de 1'Ovaire de Chiennes ayant 1'Extirpa-
tion partielle ou totale de 1'Appareil Thyro-Parathyroi'dien," C. R. de la Soc.
de Biol., vol. Ixvi., 1910.
5 Gottschau, " Ueber Nebennieren der Saiigethiere," &c., Sitz.-Ber. d.
phys. med. Gesell. zu Wiirzburg, vol. xvii.-xviii., 1882.
6 Stilling, " Zur Anatomic der Nebennieren," Arch. f. Mikr. Anat,t
vol. lii., 1898.
ORGANS OF INTERNAL SECRETION 351
disappears, while characteristic cells known as " summer cells "
become developed. Bulloch and Sequeira l state that in cases
of children with carcinomata of the supra-renals, this is asso-
ciated with premature development of the genital organs and
the accessory generative glands.
GENERAL CONCLUSIONS REGARDING THE INTERNAL SECRETIONS
OF THE OVARY AND THE TESTIS
It will be convenient at this point to summarise the con-
clusions which have been tentatively arrived at concerning the
nature and purpose of the internal secretions of the ovary and
the testis.
The mammalian ovary, in addition to its oogenetic function,
is an organ elaborating a chemical substance or substances
which react on the general metabolism and control the nutrition
of the uterus. The secretion is probably produced by the cells
of the follicular epithelium, or by the interstitial cells of the
stroma, or, perhaps, by both combined.2 It is formed in greater
or less quantity at all times, but is produced in increased
abundance at certain recurrent periods, when it brings about
those conditions of growth and hypersemia which characterise
the prooestrous processes. It is at these periods also, in typical
cases, that the follicles become mature. After ovulation, which
occurs during oestrus, the secretory cells of the ovary show still
greater activity, and become converted by a process of simple
hypertrophy into the luteal cells of the corpus luteum. If the
ovum is fertilised, these cells continue to increase in size until
nearly mid-pregnancy (or, in some animals, a somewhat earlier
period), when they exhibit signs of degeneration. If pregnancy
1 Bulloch and Sequeira, "On the Relation of the Supra-renal Capsules
to the Sexual Organs," Trans. Path. Soc., vol. Ivi., 1905.
2 Limon (loc. cit.) suggested, as a result of his experiments in grafting,
that the ovarian secretion is elaborated by the interstitial cells. It should
here be remembered that the follicular epithelial and interstitial cells are
almost certainly identical by origin, and so probably similar potentially
(p. 124), and that both of these cellular elements have been described as
taking part in the formation of the corpus luteum (p. 148) ; and also, that
those interstitial cells which do not form part of the corpus luteum have
been stated to undergo an independent hypertrophy during pregnancy
(p. 345).
352 THE PHYSIOLOGY OF REPRODUCTION
does not supervene, the luteal cells begin to degenerate at a
much earlier period and without attaining their full development.
The pronounced hypertrophy of the follicular epithelial and
interstitial cells, which takes place at the beginning of pregnancy,
is directly correlated with a nearly simultaneous hypertrophy
on the part of the uterine wall. The corpus luteum, therefore,
is to be regarded as an essential factor in maintaining the raised
nutrition of the uterus during the earlier stages of the period of
gestation. When the later part of this period is reached, the
ovarian secretion has probably been already formed in sufficient
quantity to prevent the uterus from lapsing into the normal
condition until the end of pregnancy. It is to be noted, how-
ever, that fibrous degeneration has been described in the
maternal placenta in the later stages of its existence.
Thus the ovaries pass through a series of cyclical changes
which are directly correlated with those undergone by the
uterus. Moreover, the uterus atrophies after ovariotomy.
It seems probable that this close co-ordination between the
ovarian and uterine functions arose very gradually in evolu-
tionary history, and it may be that in the aplacental mammals
we have in existence at the present day an intermediate stage
in the development of this relation. Starling 1 has suggested
that the internal secretions, or hormones generally, arose at first
as products of ordinary metabolic activity in certain particular
tissues, and that the evolution of the various cases of chemical
correlation between different organs in the body came into
existence, not by the production on the part of certain tissues
of special substances acting as chemical messengers, but by
the acquisition of a specific sensibility on the part of other
functionally related tissues. It is no doubt possible that the
chemical co-ordination of the ovarian and uterine activities
arose partly in this way ; but, on the other hand, the definite
character of certain of the cyclical changes which take place in
the ovary, and particularly those which relate to the formation
of the corpus luteum, points to the conclusion that the secretory
function of the ovary has been perfected, or at any rate, has
undergone great development in the phylogenetic history of the
1 Starling, " The Chemical Co-ordination of the Activities of the Body,"
Science Progress, vol. i. (April) 1907.
ORGANS OF INTERNAL SECRETION 353
Mammalia, though it no doubt existed previously in a minor
degree.
As to whether the ovary elaborates more than one specific
substance acting as a chemical excitant, nothing is definitely
known, but the composition of the corpus luteum (which ~T3
different from that of the rest of the ovary) indicates that the
formation of this structure is accompanied by a change in the
nature of the ovarian secretion. Lastly, it is possible that
the influence of the ovary upon the metabolism is due partly
to this organ being excretory as well as secretory in function,
but there is no evidence that this is actually the case.
The fact that the testis is an organ of internal secretion
seems now to be definitely proved. This secretion is probably
formed throughout the entire reproductive period of an animal's
life ; but, in those animals which experience a periodic rut, it is
no doubt at this season that the testicular hormone is produced
in greatest abundance. The development of the prostate and
the secondary sexual characters, not to mention the growth of
the testes themselves, is convincing evidence that this is the case.
THE EFFECTS OF CASTRATION UPON THE GENERAL
METABOLISM
In view of the facts referred to above it is almost self-evident
that castration must exercise some influence upon the general
metabolism of the body since it produces such marked effects
upon the primary and secondary sexual characters. Moreover,
it is commonly asserted that the removal of the reproductive
glands causes a tendency towards obesity both in Man and
animals, but it is not quite clear whether this occurs as a direct
or an indirect consequence of castration. The deposition of fat
which is sometimes seen to take place after the menopause
may be regarded as further evidence of a connection between
the functional ovaries and the general metabolism.
The existence of such a functional correlation is shown more
clearly by the effects of ovariotomy upon the bone disease
known as osteomalacia.1 The ovaries undoubtedly exert a
1 In one case of osteomalacia Kronig removed the ovaries and trans-
planted them on to the peritoneum. The result was immediately beneficial ;
Z
354 THE PHYSIOLOGY OF REPRODUCTION
marked influence over the phosphorus metabolism, and the
improvement which sets in after the removal of these organs in
cases of osteomalacia is apparently brought about by a re-
tention of the earthy phosphates whereby the skeletal tissues
acquire their normal rigidity. Unfortunately, the experimental
work which has so far been done upon the phosphorus meta-
bolism in normal and castrated animals is too contradictory to
admit of the deduction of any conclusions that are calculated
to throw light upon the phenomena of osteomalacia.1
The protein metabolism of castrated animals has been in-
vestigated by Liithje,2 who records no changes as a consequence
of the removal of the generative glands. Certain other in-
vestigators, as a result of shorter series of experiments, have
obtained trifling effects, sometimes showing a slight increase
in the nitrogenous output and sometimes a diminution.3
Experiments upon the respiratory exchange have been
almost equally inconclusive, and have so far failed to show any
constant alteration as a consequence of castration. This
question is discussed at some length by van Noorden,4 who
calls attention to the necessity for distinguishing whether the
total daily metabolism, which in some cases has been shown
to become diminished after castration, does so in consequence
of a variation in temperament (or greater tendency towards
physical repose), or whether the oxidation of the resting cell
(i.e. the fundamental metabolism) is reduced. He is disposed
to believe that the marked diminution in the respiratory ex-
change which has been observed in some animals after castration
is probably due to a greater indolence, and is, therefore, an
indirect result. Moreover, he points out that, in the case of
but with the return of menstruation, which followed after about two months,
the symptoms of the disease are said to have reasserted themselves (Stuttgart
Medical Congress, Zeit. f. GyndTc., 1996). See also Fraenkel, " Ovarialan-
tikorper und Osteomalacia," Munch. Med. Wochenschr., No. 25, 1908.
1 Van Noorden, Metabolism and Practical Medicine, English Edition, edited
by Walker Hall, vol. i., London, 1907. According to Wallart, " Ueber das
Verhalten der interstiellen Eierstocksdriise bei Osteomalacia," Zeitsch. /.
Geb. und Gyncik., vol. Ixi., 1908, osteomalacia is correlated with an increase
of the interstitial cells in the ovary.
2 Liithje, " Ueber die Kastration und ihre Folgen," Experim. Archiv,
vol. xlviii., 1902, and vol. 1., 1903.
8 Van Noorden, loc. cit. 4 Ibid.
ORGANS OF INTERNAL SECRETION 355
Liithje's castrated dogs, which did not exhibit any change
from their normal habits and movements, there was no diminu-
tion in the gaseous exchange as compared with control animals.
Loewy and Richter,1 however, have arrived at different
conclusions, finding pronounced reduction in the respiratory
metabolism of castrated dogs of both sexes. Furthermore,
these investigators found that after feeding the female animals
upon ovarian substances there was a great increase in the
metabolism, a castrated bitch showing an increase of from
30 to 50 per cent, above the normal values observed before the
operation. Testicular substance had no influence upon any
of the castrated animals, while normal animals did not react at
all either to ovarian or to testicular extracts. Loewy and
Richter suggest that the ovaries produce a specific substance
which promotes oxidation in the body.
Zuntz 2 has investigated the gaseous metabolism in four
castrated women, and found that it lay within the limits of
the normal. It is to be noted that neither of these women
showed any tendency to corpulence. These observations
support the view that when castrated animals show a reduction
in the respiratory exchange, this is an indirect effect resulting
from greater indolence of disposition. On this view also, the
tendency towards a deposition of fat on the part of many
castrated animals is to be attributed to the same cause.
Dr. Cramer,3 working in conjunction with the author, has
lately investigated the respiratory metabolism of a number
of rats whose ovaries had been removed some time previously,
and in these animals it was found that the gaseous exchange
lay within the limits of the normal, thus confirming Zuntz 'a
experience with castrated women. It is possible, however,
that the results of castration were obscured by other factors.
In this investigation the apparatus employed by Haldane and
Priestley was used in preference to that of Zuntz. We did
not observe any marked tendency to deposition of fat in the
castrated rats.
1 Loewy and Eichter, " Sexual-Funktion und Stoffwechsel," Arch. f.
Phys., Supplement, 1899.
2 Zuntz, "Gaswechsel bei Kastrierten Frauen," Verhandl. d. Gyntik.
Oesell., Berlin, 1904. See also Deutsch. Zeitschr. f. Chir., vol. 65, 1908.
3 Cramer and Marshall. MS. unpublished.
356 THE PHYSIOLOGY OF REPRODUCTION
Furthermore, it is to be noted that, according to Magnus -
Levy and Falk,1 the period of puberty in boys and girls is not
associated with any increase in the gaseous metabolism.
Certain further experiments upon the effects of administer-
ing ovarian extract may also be referred to here. Neumann
and Vas 2 record losses of nitrogen, phosphorus pentoxide, and
calcium monoxide after injecting glycerine extract of ovary
subcutaneonsly. Loewy 3 and Neumann found no change in
the nitrogen metabolism in castrated animals after administering
ovarian extracts, but Neumann observed a loss of phosphorus
pentoxide and calcium monoxide in the faeces. Certain other
less satisfactory experiments, dealing with more or less con-
tradictory observations, are briefly referred to by van Noorden.
The influence of castration upon the blood has formed the
subject of a research by Breuer and Seiler,4 who employed
bitches whose ovaries were removed shortly after puberty.
They record marked diminution in the haemoglobin and the red
cells.5
In concluding this brief summary of the recorded results of
castration upon the metabolism, the necessity for further in-
vestigation must be emphasised, since it is hardly possible that
the totality of the effects produced is of as slight a nature as the
experimental evidence at present seems to indicate.6
1 Magnus-Levy and Falk, " Lungengaswechsel des Menschen," Arch. f.
Phys., Supplement, 1899.
2 Neumann and Vas, "Einfluss der Ovariumpraparate auf den Stoff-
wechsel," Monatsschr. f. Geburtsh. u. Gyndk., vol. xv., 1902.
3 Loewy, "Ueber den Einfluss des Oophorins," Berl. klin. Wochenschr.,
1899.
4 Breuer and Seiler, " Einfluss der Kastration auf den Blutbefund weib-
licher Tiere," Experim. Archiv, vol. 1., 1903.
5 It has also been stated that castration may improve the quality of the
milk (Oceanu and Babes, " Les Effets Physiologiques de I'Ovariotomie chez
la Chevre," G. R. de I'Acad. des Sciences, vol. cxl., 1905). For some
account of the effects of disease in the ovaries and other reproductive organs
upon the rest of the body, see Wilson, "The Reciprocal Relations between
the Affections of the Uterus and its Appendages upon the Rest of the Body,"
(Lancet, Part II., Nov. 1906). Further references are given in this paper.
6 For the effects of hypophysectomy see Crowe, Gushing, and Homans,
"Experimental Hypophysectomy" (Johns Hopkins Hosp. Bull., vol. xxi.,
May 1910). These investigators found that partial removal of the anterior
lobe caused hypoplasia of the generative organs in adult dogs, but persistent
infantilism if operated on before puberty.
CHAPTER X1
FCETAL NUTRITION: THE PLACENTA
" Birth ... is commonly considered as the point at which we begin
to live. More truly it is the point at which we leave off knowing how to
live. . . . Not but what before birth there have been unsettled convictions
(more's the pity) with not a few." — SAMUEL BUTLER.
PART I
THE PLACENTA AS AN ORGAN OF NUTRITION
I. HISTORICAL SURVEY
THE mammalian ovum, in all except the Monotremata, is small
and does not contain a sufficient supply of nutriment for the
developing embryo. It is retained for a longer or shorter period
in the uterus, where, by special modifications of the uterine
mucosa and a part of the ovum, the placenta is formed, and a
transmission of nutriment from the mother to the embryo is
made possible. The changes in the maternal and embryonic
tissues vary greatly in the several orders, and even in groups of
the same order, but in all they are sufficiently complicated to
render their explanation a matter of great difficulty. It is
doubtful if any anatomical structure has given rise to keener or
more prolonged controversies than the placenta.
We owe to Harvey 2 the conception of the placenta as an
organ elaborating from the maternal blood the aliment necessary
for the growth and development of the foetus. He was the first
to reject the " subtleties and fanciful conjectures " on embryonic
development, and to advocate and practise direct and diligent
observation. But for a century after his death the placenta
received little attention. With the introduction of the micro-
scope the attention of biologists was directed towards the origin
and development of the embryo, and it was then that the
ovarian vesicles and spermatozoa were first observed.
1 By James Lochhead.
2 Harvey, The Generation of Animals, London, 1651.
357
358 THE PHYSIOLOGY OF REPRODUCTION
In the second half of the eighteenth century were pub-
lished the researches of John and William Hunter on the human
placenta, important not only in themselves, but as destined
to set agoing the vast amount of work done in the first half
of the nineteenth century. John Hunter l stated that the
maternal blood circulated through the placenta, and this view,
which, according to Waldeyer,2 had formerly been held by Vater
and Noortwyk, though the latter at least believed in the com-
munication of the maternal and foetal circulations, was sup-
ported by the subsequent dissection of injected placenta by
John Hunter and his brother. The statement of the former
that " the blood of the placenta is detached from the common
circulation of the mother, moves through the placenta, and is
then returned back into the circulation of the mother/' gave
rise later to a considerable amount of discussion. They showed
that the decidua was uterine and not foetal, and the decidua
reflexa was first figured in one of William Hunter's plates.3
It is remarkable that John Hunter did not recognise the
placenta as the organ of fcetal respiration. A century before,
Mayow 4 had declared that the placenta functioned as a fcetal
lung, the umbilical vessels taking up the nitro-aerial gas (oxygen)
and carrying it to the foetus. This view was adopted by Ray,5
who compared the villi lying in the maternal sinuses to the
gills of a fish in the water. The first to take up Priestley's
discovery of oxygen, and state definitely that it was oxygen that
went constantly from mother to foetus, and whose absence
caused festal asphyxia, was Girtanner 6 in 1794. But all doubt
was not removed till, in 1874, the spectroscopic bands of oxy-
hsemoglobin were demonstrated in the umbilical vein of a guinea-
pig by Albert Schmidt, a pupil of Preyer.6
The work of the brothers Hunter was carried on by Weber,
Goodsir, Coste, Eschricht, Reid, and others. Of the many
investigations, none had such an important influence as the
1 J. Hunter, Observations on Certain Parts of the Animal Economy, Edit,
by Palmer, vol. iv.
2 Waldeyer, " Bemerkungen iiber den Bail der Menschen- uud Affen-
placenta," Arch. f. mikr. Anat., vol. xxxv., 1890.
3 W. Hunter, Anatomy of the Human Gravid Uterus, Birmingham, 1777.
4 Mayow, Tractus Tertius de Respiratione Foetus in Utero, .1674.
5 Kay, The Wisdom of God in the Creation, 12th Edit., 1754.
6 See Preyer's Specielle Physiologie des Embryo, 1883.
FCETAL NUTRITION: THE PLACENTA 359
researches of Goodsir.1 He first studied the placental cells with
regard to their function. His predecessors had spoken in the
vaguest terms of the passage of nutriment from mother to foetus,
but Goodsir had definite ideas. He described the villi as having_
two covering layers of cells, an external system belonging to the
decidua, and an internal belonging to the chorion. As to their
function, he says : " The external cells separate from the blood
of the mother the matter destined for the blood of the foetus, they
are secreting ; the internal cells absorb the matter secreted by
the agency of the external cells." Thus we have the active part
of placental metabolism referred for the first time to the cells of
the villi.
The importance of the intervillous spaces for fcetal nutrition
was first emphasised by Weber,2 and they were the subject of
close attention. The Hunterian doctrine that in the human
placenta they contained blood was not yet established, and
their mode of development gave rise to a long-continued con-
troversy. John Hunter considered them outwith the maternal
vascular system, and his view was supported by Owen,3 Kolliker,4
and Farre.5 Weber and Reid 6 held that the spaces were
bounded by a thin maternal membrane, and Goodsir described
two layers of maternal tissue between the blood in the*sinuses
and the vessels of the villi.
The investigation of the intervillous spaces and the
epithelial investment of the villi was carried on by Turner,
Ercolani, Langhans, and many others. Turner 7 and Waldeyer
looked on the intervillous spaces as dilated maternal capillaries ;
but while Turner held that the villi, at least in part, pene-
trated their endothelium, Waldeyer supposed that they pushed
the endothelium before them, and so got a covering of this
1 Goodsir, Anatomical and Pathological Observations, Edinburgh, 1845.
2 See Wagner's Elements of Physiology, translated by Willis, London,
1841.
:J See Note in John Hunter's Collected Works, Edit, by Palmer, vol. iv.
4 Kolliker, Entwicklungsgeschichte, 1861, 1884, &c.
:> See Tod's Cyclopedia, Article " Uterus," 1858.
6 He id, " On the Anatomical Kelations of the Blood- Vessels of the Mother
to those of the Foetus in the Human Species," Edinburgh Medical and
Surgical Journal, vol. Iv., 1841.
7 Turner, "Some General Observations on the Placenta," &c., Journal of
Anatomy and Physiology, vol. xi., 1877.
360 THE PHYSIOLOGY OF REPRODUCTION
maternal layer. Langhans 1 regarded the spaces as formed
by that part of the lumen of the uterus which lay between the
surface of the mucosa and the chorion, and thought that the
villi by eroding vessels came to be bathed in extravasations of
maternal blood. Klebs 2 considered them to be lymph-spaces,
and therefore extra-vascular ; and Jassinsky 3 described them as
being formed by the penetration of the villi into the maternal
glands, whose epithelium came to clothe the villi externally.
Now it has been proved from the examination of early ova
that the intervillous spaces are entirely foetal and are formed
in the epiblast.
The investigations of Langhans proved to be the turning-
point in the controversy regarding the investment of the villi.
He showed that it consisted in the earlier stages of pregnancy
of a double covering, a deep layer of cells (Langhans' layer),
and superficially a mass of " canalised fibrin/' The presence
of fibrin had been noted by Weber and several of his successors ;
Winkler 4 proved it to be a constant phenomenon, and gave it
the name " Schlussplatte " ; but it was Langhans who first de-
scribed its relations, and suggested its probable origin from the
fcetal epiblast. The cellular layer, according to Langhans, was
mesoblastic. Kastschenko 5 first described both layers as
epiblastic, and showed that the outer layer was a syncytium
or mass of nucleated protoplasm without cell-boundaries. Such
investigations led to the feeling that the structure of the placenta
could only be understood by tracing its development from very
early periods of gestation. Hence the search for and examina-
tion of young human ova were stimulated, and the study of the
uterine condition in age-series of pregnant animals was begun.
Up to this time the chief controversies had raged around the
human placenta. Comparative placenta tion had engaged the
1 Langhans, " Untersuchungen iiber die menschliche Placenta," Arch,
f. Anat. u. PhysioL, anat. Abth., 1877.
2 Klebs (E.), " Zur vergleichende Anatomic der Placenta," Arch. f. mikr,
Anat., vol. xxxvii., 1891.
3 Jassinsky, "Zur Lehre iiber die Struktur der Placenta," Virchow's
Arch.,\o\. xl., 1867.
4 Winkler (F. N.), "Zur Kenntnis der menschlichen Placenta," Arch. f.
Gynak., vol. iv., 1872.
5 Kastschenko, "Das menschliche Chorionepithel und dessen Rolle bei
der Histogenese der Placenta," Arch. f. Anat. u. Phys., anat. Abth., 1885.
FCETAL NUTRITION: THE PLACENTA 361
attention of few morphologists, among whom Turner, the
" grand-master of placental research " (Hubrecht 1), was facile
princeps. But within recent years investigations • have been
carried out on many orders of placental mammals. Of these
the most important are the researches of Duval and HubrecEt7
which have established that the discoid placenta is essentially
" a maternal haemorrhage encysted by foetal elements."
II. STRUCTURE AND FUNCTIONS OP THE EPITHELIAL
INVESTMENT OF THE VILLI
The cellular layer of the villi is a temporary structure, and
disappears to a great extent comparatively early in pregnancy.
It is generally looked on as the mother zone of the outer syncytial
layer. Strahl 2 states, however, that in one of the new-world
apes it is not present at a stage as early as that of Peters' human
ovum, though a thick syncytial layer is present. Processes of it
precede the mesoblastic outgrowths in the formation of the villi,
and by a special proliferation of the cells at the tips of the villi,
the " Zellsaulen " of Langhans, an attachment to the decidua
is effected. While present, the cellular layer lies in the path
by which the nutriment for the foetus is carried to the villous
capillaries, but it is not known whether it exerts any metabolic
influence. Peters has suggested, without any very definite
evidence, that it may have a coagulating action on maternal
blood, necessitating the interposition of the syncytial layer.
The syncytium is more permanent. In the earliest human
ovum yet examined it already constitutes a considerable mass,
and a similar thickening over the whole or part of the circum-
ference of the blastocyst occurs early in all the Decidua ta.
Where a decidua reflexa exists, the early proliferation appears to
be related to the excavation of the cavity in which the ovum lies.
In discoid placentae the mass is vacuolated, and maternal blood
is contained in the lacunae. In the later stages of pregnancy it
forms an attenuated membrane over the villi, and may wholly
1 Hubrecht, "The Placentation of Erinaceus europceus," Quar. Jour.
Micr. Sci., vol. xxx., 1889.
2 Strahl, "Ueber Placentarsyncytien," Anat. Anz., vol. xxix., Erganz-
ungsch., 1906.
362 THE PHYSIOLOGY OF REPRODUCTION
disappear at parts. The nuclei are numerous, and most of the
authorities agree on the absence of mitoses, some holding that
they divide directly, others that they have lost the power of
division. The protoplasm has a foam-like structure, and in
Man it is condensed superficially to form a layer which bears the
" Biirstenbesatz " or striated border (Fig. 75). This consists,
as seen in fixed specimens, of a series of fine striae running per-
pendicularly to the surface, and its structure and function have
been much discussed since it was first described by Minot.1
I Si I'
'•2fr«F^ _
&.
#: ^
.;^;?*A *
FIG. 75. — Part of an early human chorionic villus. (From Hofbauer's
Biologie der menschlichen Plazenta, Braumiiller. )
b, Biirstenbesatz with basal corpuscles ; s, syncytium ; I, Langhans' layer,
one cell dividing mitotically (I'}.
Some have denied its existence during life, and ascribed it
wholly to the method of preparation. But Hofbauer 2 has
shown that the fresher a specimen is when obtained, the easier
it is to demonstrate the striae by methods of staining, and,
therefore, it is probably a vital structure. Kastschenko looked
on the stria3 as fine hairs which projected from the surface of
the cells, and by their vibrations created a stream in the maternal
blood of the intervillous spaces. In specimens stained with
iron-hsematoxylin, knobs may be seen at the bases — basal
corpuscles or blepharoblasts — and they may constitute the
1 Minot, "Uterus and Embryo," Jour, of MorphoL, vol. xi., 1889.
2 Hofbauer, Biologie der menschlichen Plazenta, Leipzig, 1905.
FCETAL NUTRITION: THE PLACENTA 363
motor centre for the ciliary beats. But no movements
have yet been observed, and von Lenhossek 1 calls them
" stereozilien," or stationary cilia, suggesting that they may
help to break down vessel-walls during the burrowing of the
syncytium into the serotina. Sometimes they appear not to
project free on the surface but to lie in the superficial stratum ;
then lighter and darker striae alternate, and it is this appearance
which has led to the name " striated edge." Bonnet 2 in-
geniously remarks that it proves the fo3tal origin of the syncytium,
because, if it were uterine, the free edge would be formed by the
bases of maternal cells, and they could not possess a " Bursten-
besatz." The same appearance has been noted in intestinal
epithelium, but its significance is unknown. In the placenta
Graf v. Spee 3 attributes the appearance to the teasing out of
the surface of the protoplasm, and looks on it as evidence of a
strong flow of fluid through the syncytium. It has also been
suggested that the thin rods may be hollow and act as pores by
which nutriment may enter the syncytium, or by which a
secretion of the syncytium may pour out in order to prepare the
constituents of the maternal blood for their transference to
the foetus.
It is still undecided whether the syncytium possesses
amoeboid motility. V. Lenhossek examined a human ovum
several minutes after its removal from the uterus and observed,
as has already been stated, no ciliary movements ; but he con-
sidered it not improbable that the syncytium underwent changes
of form. Hofbauer tried unsuccessfully to demonstrate such
movements in a specimen examined immediately after its
removal.
The core in young villi consists of a matrix, homogeneous
or delicately fibrillated. In it are placed the blood-vessels
and connective-tissue corpuscles with long branching processes,
which form a network in the matrix, and probably provide a
series of lymph-channels. Kastschenko also described special
1 V. Lenhossek, Verhandl. d. anat. Kongresses in Halle, 1902. See
Centralbl.f. Gynak., 1904, Nr. 7.
2 Bonnet, " tiber Syncytien," &c., Monatsschr. f. Geburtsh. u. Gynak.,
vol. xviii., 1903.
3 Graf v. Spee, " Neue Beobachtungen iiber sehr friihe Entwickelungs-
stufen des menschlichen Eies," Arch. f. Anat. u. Phys., anat. Abth., 1896.
364 THE PHYSIOLOGY OF REPRODUCTION
cells, with large nuclei, which he took to be wandering cells.
But Lenhossek proved that they existed before leucocytes or
lymph-cells appeared, and must therefore be formed in the villi
and derived from mesoblastic cells. Hofbauer has observed them
also in the lumen of the foetal vessels, and suggests a possible
transformation to leucocytes.
Our ideas upon the function of syncytia are largely based on
the investigations of His : 1 " They are not really specific tissue
structures, but tissue conditions requiring definite phases of
protoplasmic vitality. They occur along with a high degree of
activity — with increased absorption and action on material—
as well as with increased motility. Favourable conditions of
nutrition form the fundamental condition for the existence of
syncytia, and such conditions are certainly well offered in the
uterus." At the present time the syncytium is regarded as
of the highest importance in foetal nutrition. Strahl2 and
Heinricius,3 noting its gradual and progressive diminution as
pregnancy advanced, supposed that it formed a part of the
nutriment for the embryo, but this idea has not been adopted.
The general theory is that it is essential in maintaining the
interchange of material between mother and foetus. The sub-
stances necessary for the building up of the foetal body may be
divided into two groups — diffusible and non-diffusible. The
passage of the former can be explained by physical laws, but it
is different with the non-diffusible or colloid substances. This is
a difficulty which does not belong to the placenta alone, but to
every organ of the body, and authorities are divided between
two theories, the mechanical and the vital. The supporters of
the mechanical theory hold that all the processes occurring in
the placenta are possible by the laws of filtration and osmosis,
and they have carried out numerous experiments to prove
that substances in solution may pass across the placenta in
both directions. Others, paying special attention to the nature
of the barrier formed by the epithelial covering of the villi,
1 His, " Die Umschliessung der menschl. Frucht wahrend der friihesten
Zeit der Schwangerschaft," Arch. f. Anat. u. Phys., anat. Abth., 1897.
2 Strahl, "Der Ban der Hundeplacenta," Arch. f. Anat. u. Phys., anat.
Abth., 1890.
3 Heinricius, " Ueber die Entwicklung und Struktur der Placenta beim
Hnnde,"Arch.f. mikr. Anat., vol. xxxiii., 1889.
HETAL NUTRITION: THE PLACENTA 365
deny that by such physical processes the non-diffusible sub-
stances with large molecules, e.g. haemoglobin and other blood
proteins, can be absorbed by the syncytium. They postulate
a vital action on the part of the cells, by which the necessary
material is selected by the syncytium, and altered to a form-
in which it may be transmitted to the feetal circulation. It is
not yet settled whether the activity of the syncytium is due to a
phagocytic power or to an enzyme action.
There is a third theory regarding the transmission of nutritive
material from the mother to the foetus, viz. by the actual
passage of maternal leucocytes, charged with nutriment, from
the one circulation to the other. This theory was first ad-
vocated by Rauber l as the result of microscopic investigations,
and he instanced, as further evidence in its favour, the greater
number of leucocytes in the blood of the umbilical vein than
in that of the artery. This view, which explained satisfactorily
the passage of non-diffusible materials, subsequently received
wide support. Thus Wiener 2 said : " It may be held as nearly
without doubt that leucocytes cross from the maternal to the
feetal blood/' and Preyer 3 considered the passage of leucocytes
" indisputable/' The first objection was raised in a paper by
Paterson.4 In it he recorded three cases of pregnancy com-
plicated by leucocythsemia in the mother, and stated that the
infants appeared quite normal and healthy, and their blood
was of the usual colour and not white like the mothers'. These
results were corroborated in similar cases by Cameron 5 and
Sanger,6 who actually counted the foetal leucocytes and found
no increase. These observations, and the inability of subse-
quent investigators to demonstrate healthy leucocytes in the
tissues intervening between the maternal and foetal blood,
have led to the abandonment of Rauber 's theory.
1 Eauber, Ueber den Ursprung der Milch und die Erndhrung der Frucht
im allgemeinen, Leipzig, 1879. Also ZooL Anz.t No. 70.
2 Wiener, " Die Ernahrung des Fotus," Samml. Klin. Vortrdge, No. 290.
3 Preyer, Specielle Physiologie des Embryo, 1883.
4 Paterson, "Cases of Acute Leucocythaemia in connection with Preg-
nancy," Edinburgh Med. Jour., 1870.
5 Cameron, " The Influence of Leucaemia upon Pregnancy," Internat. Jour,
of the Med. Sc., 1888.
6 Sanger, " Ueber Leukamie bei Schwangeren urid angeborene Leukamie,"
Arch. f. Gyndk,, vol. xxxiii., 1888.
366 THE PHYSIOLOGY OF REPRODUCTION
But though maternal leucocytes do not pass as such straight
into the foetal blood, they may be important in another way.
In Ruminants, Bonnet l has drawn attention to the enormous
number of degenerated leucocytes in the uterine milk, and
demonstrated their absorption by the ectoderm, and similar
observations have been recorded in Carnivores. In these orders
leucocytes undoubtedly form a part of the embryonic nutriment.
In the rest of the deciduate Mammals they seem to play a less
important part.
III. THE DECIDUA
In the uterine mucosa during pregnancy the most noticeable
change occurs in the interglandular tissue of discoid placentae,
in which decidual cells are formed. Various opinions have been
held regarding their origin. Langhans, Hennig,2 and others
held that they were enlarged and modified leucocytes, but they
could not support their theory by direct observation. Overlach 3
and Frommel 4 described them as modified glandular cells, but
there is no doubt that the true origin is, as Creighton 5 first
suggested, from the interglandular tissue of the mucosa. This
consists of connective tissue of an embryonic type, which
allows of a rapid transformation of its cellular elements.
Masquelin and Swaen 6 demonstrated this mode of origin in
Rodents, and were supported by Minot, and Hart and Gulland.7
Leopold's studies of early ova showed that the same origin
was most probable in Man, and Peters described in the mucosa
next the ovum connective tissue cells undergoing a decidual
transformation. Their first appearance in the superficial layers
1 Bonnet, " Uber Embryotrophe," Deuts. med. Woch., 1899.
2 Hennig, Studien iiber den Ban der menschlichen Placenta, &c., Leipzig,
1872.
3 Overlach, "Die pseudomenstruirende Mucosa Uteri nach akuter Phos-
phorvergiftung," Arch. f. mikr. Anat., vol. xxxv., 1885.
4 Frommel, " Beitrag zur Frage der Wachstumsrichtung der Placenta,"
Zieits. f. Geburtsh. u. Oynak., vol. xxxvi.
5 Creighton, " The Formation of the Placenta in the Guinea-pig," Jour,
of Anat. and Phys., vol. xii., 1878.
6 Masquelin and Swaen, " Premieres phases du developpement du placenta
chez le lapin," Bull, de I'Acad. roy. de Belg., 1879.
7 Hart and Gulland, " On the Structure of the Human Placenta," &c.,
Labor. Rep., Roy. Coll. of Phys., Edinburgh, vol. iv., 1892.
F(ETAL NUTRITION: THE PLACENTA 367
of the mucosa has suggested a stimulus for their formation
arising from the product of conception.1 The study of early
human specimens has effectually disproved Ercolani's 2 idea
that the uterine mucosa was first entirely destroyed by the
developing ovum, and then replaced by decidual tissue formedr
from the cells of the vessel walls. Such an endothelial pro-
liferation does, however, occur in certain animals, e.g. hedgehog
(Hubrecht 3) and bat (Nolf 4), and probably in ectopic gestation
in Man.
The rapid increase in the size and number of the decidual
cells, together with the dilatation of the blood-vessels, leads to
a great increase in the thickness of the serotina. At a certain
stage it reaches its full development, and then gradually
diminishes till, at the end of gestation, it forms only a thin
layer, and even disappears entirely at parts so that the villi
impinge on the muscular wall.
Individual decidual cells have probably a short life-history.
Even at a comparatively early period many of them are found
in various stages of hyaline degeneration, giving rise in part to
the layers of fibrin, and as pregnancy advances there is a gradual
extension of the fibrinous change. The degeneration of the
decidual tissue would seem to be due to the influence of the
foetal epiblast, as in Man it occurs much earlier and more
abundantly in the serotina and reflexa than in the vera
(Webster 5). Its gradual diminution during pregnancy in-
dicates an absorption of the decidua. That maternal tissues
do not play a large part in this absorption is probable from the
small number of leucocytes and the absence of lymph-channels
in the neighbourhood of the fibrinous masses. At the same
1 Under abnormal conditions the formation of decidual cells occurs even
although no ovum is present in the uterus, e.g. in tubal pregnancy in the
human female. Whether this indicates a chemical stimulus from the ovum,
or perhaps from the corpus luteum, effected through the blood-stream, is not
yet known (see p. 491).
2 Ercolani, " Sulla unita del tipo anatomico della placenta," Mem. delV
Accad. di Bologna, 1876.
3 Hubrecht, "The Placentation of Erinaceus europceus," Quar. Jour.
Micr. Science, vol. xxx., 1889.
4 Nolf, " Modifications de la muqueuse uterine pendant la gestation chez
le murin," Arch, de Biol., vol. xiv., 1896.
6 Webster, Human Placentation, Chicago, 1901.
368 THE PHYSIOLOGY OF REPRODUCTION
time, specialised decidual cells, which have the power of de-
stroying the rest of the decidual tissue, have been described in
the hedgehog,1 rat, and other animals. But it is now generally
accepted that the foetal ectoderm from the earliest stages of
pregnancy is able to disintegrate the cells with which it comes
in contact, and to absorb the degenerate products. To that
part of the foetal epiblast which is thus adapted for the ac-
quirement of embryonic nutriment the name of trophoblast has
been given by Hubrecht.
Along with the gradual absorption of the degenerated parts
of the decidua, and the great increase in the extent of the
serotinal surface as pregnancy advances, there is probably a
continued formation of new decidual elements. Pfannenstiel
attributes the new formation to the peri- vascular tissue, and
Webster to groups of active cells, the " Ersatz-zellen " of Klein,2
found here and there in the mucosa. Whatever their origin is,
we may see, even in the shed placenta at full time, well-formed
and apparently healthy decidual elements as well as the
fibrinous masses containing cellular fragments.
Within recent years there has been a tendency to belittle
the importance of the connective tissue elements of the placenta.
This has been largely due to the wider acceptance of the foetal
origin of the syncytium, and to the conception of the placenta as
a maternal hemorrhage circumscribed by foetal structures. But
the same idea has been encouraged by some who look on the
syncytium as maternal, and they adduce as evidence the obvious
degeneration in the decidua during the greater part of pregnancy.
Pfannenstiel maintains that decidual cells are, from the begin-
ning, degeneration forms of the connective tissue cells and are of
use only as pabulum to be absorbed by the ovum. But during
the whole of pregnancy, as mentioned above, there exist in the
placenta decidual cells which, in their appearance and staining
properties, show no resemblance to degenerated cells. From
their abundance and great specialisation they have in all likeli-
hood definite functions to perform. Their first formation dates
1 In a later memoir Hubrecht assigns to these cells, the deciduofracts of
the hedgehog, an origin from the outer layer of the trophoblast. See
foot-note, p. 470.
2 Klein, " Entwicklung und Riickbildung d. Decidua," Zeits. f. Geburtsh.
u. Gynak., vol. xxii.
FOETAL NUTRITION: THE PLACENTA 369
from the destruction of the surface epithelium when the blasto-
cyst comes in contact with the connective tissue, and the
earliest to appear are in the neighbourhood of the ovum. Their
position and general appearance in different orders suggested tp^
Turner a maternal reaction against the advance of the parasitic
ovum, and the same idea has been forced on different observers.
Fothergill l speaks of the decidua preventing the injurious in-
vasion of the uterine wall by the fcefcal elements. Chipman's 2
figures on the placenta of the rabbit show that the ectoplacenta
advances more rapidly where it encounters a vessel than where
it lies against decidual cells. Wade and Watson 3 have noted
its resemblance to young granulation tissue in the mucosa of
the Fallopian tube in an early ec topic pregnancy. Bryce and
Teacher,4 in their description of the youngest human ovum yet
examined, say : " The decidua formation is a process of a con-
servative nature, by which, during the early months of pregnancy,
the activities of the trophoblast are limited and controlled until
such time as placenta tion is complete." Whether or not the
decidua forms the protection to the mother, there is increasing
evidence that the trophoblast does not invade the decidua to
the extent supposed by the older authorities. This was first
emphasised by Hubrecht in the hedgehog, and has more recently
been advocated by Webster, and by Bryce and Teacher, in Man.
Hoffmann 5 and Ahlfeld 6 considered the decidua to be of
the nature of a diffuse gland whose cells secreted a nutritive
juice for the wants of the foetus. They stated that they could
demonstrate such a secretion in the " intervillous " spaces formed
by the separation of the decidual cells ; but their observa-
tions have been discounted by the investigations of Werth,7
1 Fothergill, "Decidual Cells," Edinb. Med. Jour., vol. v., 1899.
2 Chipman, "Observations on the Placenta of the Babbit," &c., Edinb.
Roy. Coll. of Physic. Labor. Rep., vol. viii., 1903.
3 Wade and Watson (B. P.), "The Anatomy and Histology of an Early
Tubal Gestation," Jour, of Obstet. and Gynec. of the Brit. Emp., 1908.
4 Bryce and Teacher, Contributions to the Study of the Early Development
and Imbedding of the Human Ovum, Glasgow, 1908.
5 Hoffmann, " Sicherer Nachweis der sogennanten Uterinmilch beim
Menschen," Zeits. f. Geburtsh. u. Gyndk., vol. viii., 1882.
6 Ahlfeld, Berichte u. Arbeiten aus der geburtsh. Klinilc zu Giessent
Leipzig, 1883.
7 Werth, " Beitrage zur Anatomic, Physiologic, und Pathologic der
menschlichen Schwangerschaft," Arch. f. Gyndk., vol. xxii.
2A
370 THE PHYSIOLOGY OF REPRODUCTION
who showed that the spherical globules described by Hoffmann
were never present in the fresh placenta, but appeared only
after its separation, and probably consisted of droplets exuded
by the dying chorionic epithelium. It may be mentioned
here that the " boules," described by Nattan-Larrier l as an
internal secretion of the syncytium, have been thought by
many to be a post-mortem appearance.
In Rodents the decidual cells have an important and definite
part to play in synthesising and storing glycogen as a supply
of carbohydrate for the foetus. In Man also the decidual cells
contain glycogen at an early period. Fat globules infiltrate
the decidual cells of various animals at a stage when there is
no question of a fatty degeneration taking place in the cells.
Finally, the cells appear to have the power of ingesting and
decomposing erythrocytes, but their relations to the iron-
metabolism of the foetus require further study.
PART II
THE FIRST STAGES OF PREGNANCY: PLACENTAL
CLASSIFICATION
I. THE OVARIAN OVUM
WHILE still in the ovary, the ovum obtains the necessary nutri-
ment by means not yet discovered. In the Graafian follicle it
is surrounded by the zona pellucida and externally the corona
radiata. The origin of the zona pellucida has been variously
described. According to some authorities it is the thickened
outer edge of the ovum itself, a true vitelline membrane, but it
is more probably a deposit from the cells of the corona radiata.2
Its structure is almost homogeneous, but with the highest
powers of the microscope fine striae are seen running from
without inwards. Their appearance indicates the possibility
that they are pores or delicate canals by which protoplasmic
processes of the cells of the corona radiata, or a secretion of
1 Nattan-Larrier, " Fonction secretaire du placenta," Comp. Rend, de
VAcad. de Sc., vol. lii., 1900.
2 I.e., the discus proligerus, or innermost layer of follicular epithelium.
FCETAL NUTRITION: THE PLACENTA 371
these cells, may reach the ovum and nourish it (see p. 127).
Whatever the source of the food-supply of the ovum is, it not
only increases in size until it is ripe for deliverance, but stores
in its protoplasm yolk granules, the deutoplasm of Beneden,
which increase in number as the ovum approaches maturity^
The granules vary in size and number in different species, and
also in their position. They may be mingled uniformly through
the cytoplasm, or be collected at the marginal zone (sheep), or
at the periphery of the central zone (Man). During the earliest
stages of segmentation, when perhaps food is not readily acces-
sible, or a specialised form of nutriment is required, the granules
are used up.
II. THE FERTILISED OVUM AND ITS COVERINGS
When the ovum leaves the ovary it carries with it the zona
pellucida and cells of the corona radiata. After fertilisation,
which most probably occurs in all animals at the outer end of
the oviduct or Fallopian tube, the cells disappear and are re-
placed in some species by a homogeneous sticky layer of
albuminous material. According to Robinson,1 it is derived in
part from the disintegrated cells of the corona radiata, but
most of it seems to be obtained from the secretion of the
tubal and later of the uterine glands.2 It is covered by
villous tufts, which led to its designation as prochorion by
Hensen. But the tufts are merely casts of the gland-ducts, due
to the coagulation of the secretion by the use of reagents.
The investment formed by the two layers around the ovum
is very thick in Marsupials. In Ungulates it forms a thin coat,
which disappears at a comparatively early stage in the pig,
sheep, and deer. In the last named, according to BischorT, there
is no albumen layer. In Carnivores there is invariably a firm
coat of zona pellucida or albumen layer, or both, which persists,
in the dog and ferret at least, till the appearance of the primitive
streak and the commencement of the formation of the mesoderm
1 Robinson, " On the Early Stages of Development of Mammalian Ova,
and on the Formation of the Placenta," Hunterian Lectures, Jour, of Anal,
and PhysioL, vol. xxxviii., 1904.
2 Bonnet, " Ueber das Prochorion der Hundekeimblase," Anat. Anz..
vol. xiii., 1897.
372 THE PHYSIOLOGY OF REPRODUCTION
(Robinson). In Rodents there are differences. In the rabbit
(Fig. 76) the albuminous layer is well-marked while the fertilised
ovum is still in the Fallopian tube ; on the fourth day, when
the uterus is reached, it rapidly thins but remains up to the
eighth day (Assheton l). In the rat the covering disappears
early — usually about the eight-cell stage. In the mole the
FIG. 76.— Early blastocyst of the rabbit. (From Hertwig's EntwicTclungs-
geachichte des Menschen und der Wirbelthiere : by permission of Gustav
Fischer.)
a, albumen layer ; zp, zona pellucida ; t, trophoblast ; sc, segmentation
cavity ; ec, mass of embryo cells.
covering is thick, and, according to Heape,2 the albumen layer
is applied in the uterus and not in the Fallopian tube. It per-
sists, as in the shrew, till the embryonic ectoderm appears on
the surface of the ovum. In the hedgehog and bat it dis-
appears before the blastocyst is formed, and in Tupaia javanica
it may be already absent in the two-cell stage. Little is
known of it in the Primates ; in the earliest ovum investigated,
1 Assheton, " The Attachment of the Mammalian Embryo to the Walls
of the Uterus," Quar. Jour. Micr. Sci., vol. xxxvii., 1895.
2 Heape, "The Development of the Mole (Talpa europcea)," &c., Quar.
Jour. Micr. Sci., vol. xxiii., 1883.
FCETAL NUTRITION: THE PLACENTA 373
the four-cell stage of Macacus nemestrinus, it had already dis-
appeared .
With regard to its functions, there is little doubt that the
degenerating cells of the corona radiata, and later the albumen
layer, serve as food for the growing mass of the ovum in the
Fallopian tube and uterus. In the investment in the mouse,
Jenkinson 1 found nutritive substances — fat, and probably also
protein matter. In addition, Bonnet has adduced strong
evidence to show that it is absorbed by the ectoderm of the
blastodermic vesicle. In the rabbit the albumen layer forms
a tough, strong membrane enclosing at the end of the third day
the solid morula. Within the mass of cells a cavity develops
and rapidly increases by diffusion inwards of fluid. "It is
hardly conceivable that the delicate cells could cause expansion
of the tough albuminous wall. Rather the osmotic current is
more inwards than outwards, either simple or more probably
assisted by the vital activity of the cells " (Assheton). Heape
had previously pointed out that the increasing fluid must be
secreted into the interior of the blastocyst under considerable
pressure, as the vesicle remains spherical and extends the uterine
walls before it. Once inside, the fluid exerts a greater or less
hydrostatic pressure, which is counteracted by the albumen
layer, and the rupture of the vesicle is prevented. At the
beginning of the cavity formation in the morula, the cells are
not yet pressed on by the investment. Later the vesicle in-
creases in size, and the outer cells are pressed and flattened.
At the same time the albumen layer is thinned, and is soon
hardly perceptible. Finally it ruptures, and immediately after-
wards the blastodermic vesicle is flaccid, apparently from injury
to its wall.
Besides its nutritive and protective function, the investing
layer may prevent the contact of the external cells of the blasto-
dermic vesicle with the cells of the uterus. Only when it has
disappeared is fusion of the maternal and foetal elements
possible. Robinson has followed out this idea in different
Mammals. He suggests that in those animals (Carnivores,
rabbit) in which the embryonic ectoderm reaches the surface,
1 Jenkinson, "Observations on the Physiology and Histology of the
Placenta of the Mouse," Tijd. Nederl. Dierk., Ver. ii., Dl. 7.
374 THE PHYSIOLOGY OF REPRODUCTION
the albumen layer prevents contact with the uterine wall till
differentiation of the ectodermal cells has taken place to such
an extent that they are no longer disposed to fuse with the
uterine tissues. In those in which the embryonic ectoderm
never reaches the surface (mouse, guinea-pig, hedgehog, bat,
probably Primates), the investment disappears before the
bias tula is attained.
With the disappearance of the zona, the developing ovum
lies naked in the Fallopian tube or the uterus. It takes some
time to complete the journey along the tube — about eighty
hours in the rabbit, and a little longer in the sheep. For a
further period it remains unattached in the uterine cavity,
and then, by processes which vary in different orders, it obtains
attachment — loose in Marsupials and firmer in the other orders.
At first each blastomere is nourished separately ; but when
the blastocyst is formed, the greater part of its outer layer is
set aside to look after the nutrition of the whole, and takes no
share in the formation of the embryo or amnion. To that part
Hubrecht gave the name of trophoblast, and the term has been
generally accepted. Already, before the embryo is elaborated,
provision is in this way made for its maintenance.
III. THE UTERINE MUCOSA
While the ovum is still in the oviduct, no obvious changes
occur in the uterus itself. In the sheep, Assheton * detected no
difference except an increase in the number of the leucocytes.
There was no sign of activity in the uterine glands or blood-
vessels. When the ovum reaches the uterus changes begin—
dilatation of blood-vessels and lymphatics, widening and in-
creased tortuosity of glands, disappearance of cilia from the
surface epithelium. The whole mucosa is soft and cedematous,
and there may even be a transudation of lymph into the uterine
cavity, which is mingled with the glandular secretion to form
a supply of nutriment for the ovum before attachment. Great
1 Assheton, "The Morphology of the Ungulate Placenta," &c., Phil.
Trans. Roy. Soc., London, Ser. B., vol. cxcviii., 1906.
FCETAL NUTRITION: THE PLACENTA 375
differences, however, occur, and it is more convenient to de-
scribe the changes in the uterine mucosa in each order.
IV. PLACENTAL CLASSIFICATION
At the outset we are beset with the difficulty of grouping
Mammals in such a way as to show how the variations in the
anatomy and physiology of the placenta have been evolved.
Well-marked differences, such as occur in other organs and
serve to differentiate Mammals into certain orders, are not
always to be observed in their placentae. In widely diverging
groups there may be striking similarities in placentation, while
great differences may exist in closely related types. On this
account the most satisfactory, and indeed the only possible,
classification of Mammals for our purpose is one based on their
placental characters. Such a classification was introduced by
Huxley l in 1864. He divided Mammals into two great sections
according as their placentae were non-deciduate or deciduate.2
In Deciduates the substance of the mucosa undergoes rapid
growth and textural modification to form decidual tissue, and
the maternal and foetal parts of the placenta become firmly
united. In Non-deciduates there is no formation of decidual
tissue, and at parturition the foetal villi are simply drawn out
like the fingers from a glove, no vascular substance from the
mother being thrown off.
In a later publication 3 Huxley attempted to arrange all
Mammals in one or other division. The Deciduata are classed
in two groups according to the external appearance of the
placenta, which is either zonary, as in Carnivora, Amphibia, and
Proboscidea ; or discoid, as in Rodentia, Insectivora, Cheiroptera,
Lemuridse, Simiadaa, and Primates. The Non-deciduata are the
Ungulata and Cetacea. The Sirenia and Edentata offer diffi-
culties. Of the latter, Manis has a diffuse placenta, Bmdypus
a poly-cotyledonary, and Orycteropus a discoid and deciduate
1 Huxley, The Elements of Comparative Anatomy, London.
2 Thirty years earlier Weber had suggested a similar division into caducous
and non-caducous ; but his terms, although accepted by von Baer and
Eschricht, were displaced by those of Huxley.
3 Huxley, Introduction to the Classification of Mammals, London, 1869.
376 THE PHYSIOLOGY OF REPRODUCTION
placenta. One of the Sirenia, the dugong, which possesses a
zonary but not deciduate placenta, illustrates a type not re-
presented at all in Huxley's classification. No maternal tissue
is lost at birth ; but, in addition, part of the fcetal tissue remains
attached to the uterus and is absorbed (Turner 1). The placenta
of the mole is not shed at birth, but becomes gradually absorbed
by the mother. For such Hubrecht 2 suggested the term
contra-deciduate.
The classification of Strahl 3 does not promise to be any
more satisfactory. He divides Mammals into two groups, one
having a " Halbplacenta " and the other a " Vollplacenta."
In the former no maternal vessels are opened and the connec-
tion is less intimate, while in the latter haemorrhages occur
during pregnancy. But in a physiological sense, the half
placenta is certainly as efficient an organ of nutrition as the
whole placenta.
In view of the recent work on the placenta, it is obvious
that Huxley's classification fails in taking no account of the
trophoblast, the most active constituent of the placenta, and
in laying too much stress on the differences at birth, i.e. on the
shedding of an organ which is of no more use, and may be con-
sidered as physiologically dead. Moreover, it would appear
that in many of the deciduate Mammals almost no maternal
tissue except blood is lost at birth, and maternal blood is also
lost in the non-deciduate sheep. A perfect classification must
take account of the structure and behaviour of the trophoblast
during the whole course, or at least the earlier part, of pregnancy.
Without it a clear insight into the processes which regulate
fcetal nutrition cannot be obtained. Robinson 4 and Assheton 5
have recently made efforts in this direction, the former em-
phasising the methods of attachment of the trophoblast to the
uterus, and the latter the anatomical condition of the tropho-
1 Turner, "On the Placentation of Halicore Dugong" Trans. Roy. Soc.
Edin., vol. xxxv., 1889.
2 Hubrecht, " Spolia Nemoris," Quar. Jour. Micr. Sci., vol. xxxvi., 1894.
3 See Hertwig, Entivicklungsgeschichte des Menschen und der Wirbelthiere,
1906.
4 Robinson, " Hunterian Lectures," loc. cit.
6 Assheton, "The Morphology of the Ungulate Placenta," Phil. Tranz,
Roy. Soc., London, Ser. B., vol. cxcviii., 1906.
FCETAL NUTRITION: THE PLACENTA 377
blast at the time of its first attachment. Hubrecht, on the
basis of Huxley's statement that Insectivora are among the
most archaic of Mammals, has investigated several members of
this order as showing probably the most ancient type of placenta,
and thus affording a starting-point for a classification. Accofct-'
ing to Huxley, the least differentiated types, the hedgehogs
and Gymnwa, occupy a central position, while shrews show
resemblances to Rodents, and Tupaice to lemurs ; moles and
Galeopitheci vary in other directions, while the whole order
shows more general relationships to Carnivores and Ungulates.
But at present these relationships are not understood. It
seems impossible to trace any connection between the placenta
of the sheep, in which there is no circulation of maternal blood
in the foetal parts of the placenta but the foetus is nourished
by uterine milk, and that of the hedgehog, in which maternal
blood circulates in the trophoblastic lacunae and forms the
main source of nutriment.
At present, we must be content with a review of the pro-
cesses occurring in several Mammals which have been more
particularly investigated, without straining to find how such
processes have arisen in the course of placental evolution.1
PART III
THE FCETAL MEMBRANES, THE YOLK-SAC,
AND THE PLACENTA
I. GENERAL ANATOMY OF THE FCETAL MEMBRANES
So far no reference has been made to the part played by the
mesoblast in the nutrition of the embryo. The placenta has
been described as an organ consisting of maternal and foetal
elements — of modified uterine mucosa, and trophoblast which
1 Throughout this chapter, the arrangement of the mammalian orders is
more in accordance with the older views of placental classification, but an
attempt has been made to emphasise the trophoblastic characteristics.
Since it was written, an important memoir has been published by Hubrecht
("Early Ontogenetic Phenomena in Mammals," Quar. Jour. Micr. Sci.,
1908), in which he follows out, in more detail than previously, his ideas
regarding the phylogeny of the placenta.
378 THE PHYSIOLOGY OF REPRODUCTION
absorbs nutritive material from the mucosa and from the
maternal blood. The nutriment serves in part for the nutrition
of the trophoblast itself, and in part for the growth and de-
velopment of the embryo. In the earliest stages there are as
yet no embryonic vessels, and the nutriment is transmitted
from cell to cell. But as the embryo increases in size and its
requirements grow in proportion, such a path becomes in-
adequate, and a vascular channel is developed in connection
with the two foetal membranes — the yolk-sac or umbilical vesicle,
and the allantois.
The mammalian yolk-sac has only a secondary importance
for the nutrition of the embryo. The blastodermic vesicle
at an early stage of development is divided into an embryonic
and a non-embryonic area. The latter is the yolk-sac which
gradually becomes folded off from the embryo. Its relations
are the same as those of the yolk-sac in Sauropsida, but the
contents are an albuminous fluid instead of yolk. It is com-
monly believed that the placental Mammals are descended from
ancestors in which the ovum had a large supply of yolk, but
that, when the fertilised ovum found a new supply of food in
the uterus, the yolk was reduced and ultimately disappeared.
At the same time the envelopes, which were developed under
the influence of the vitelline contents, have been preserved and
modified in different ways to aid uterine nutrition.1
In the early stages the development proceeds, as in birds
and reptiles, with the gradual extension of the hypoblast round
the wall of the blastocyst, which thus becomes didermic. The
mesoblast grows out between the epiblast and hypoblast,
starting at the embryonic area and gradually extending for a
variable distance round the wall of the blastocyst. Near the
embryo appears the area vasculosa, in which blood-vessels and
blood are developed from the cells of the mesoblast, while at
the same time the embryo begins to be folded off from the
yolk-sac by anterior and posterior folds. The area gradually
extends further and further round. Its outer boundary is
marked by the sinus terminalis which communicates with the
vitelline veins. The blood is brought from the dorsal aortse by a
1 According to Hubrecht's views, the mammalian ovum is not descended
from the ovum of Sauropsida.
FCETAL NUTRITION: THE PLACENTA 379
series of lateral vitelline branches. These arteries break up into
a deeper arterial network, from which the blood is collected into
the sinus terminalis and the superficial venous network, and in
this way reaches the vitelline veins and so passes to the heart.
During the spread of the mesoblast, it splits into an external"
layer or somatopleur, and an internal layer or splanchnopleur.
The former is non-vascular and adheres to the inner aspect of
the trophoblast, forming with it the diplo-trophoblast, and the
splanchnopleur is applied externally to the hypoblastic wall
of the yolk-sac. By the splitting a space is formed between the
two layers. This is the extra-embryonic ccelom, which thus
intervenes over a larger or smaller area between the diplo-tropho-
blast and the yolk-sac.
While the above changes are taking place, the allantois
grows out (on the tenth day in the rabbit) from the hind-gut
as a vesicle lined by hypoblast, and covered externally by a
layer of splanchnopleur. In some Mammals the cavity of
the allantois is not continued beyond the body-wall of the
embryo, the extra-embryonic portion consisting of a solid rod
of mesoblast. In all orders below the Primates, however,
it projects free for a time into the ccelom, and later fuses, except
in the Marsupials, with the whole or part of the outer wall of
the blastocyst. In the allantoic mesoblast many vessels are
developed, and branches extend into the projections which form
the cores of the villi. The blood is brought by two allantoic
arteries continued from the terminal bifurcation of the dorsal
aorta, and returned by one, or more rarely two, allantoic veins.
" While the placenta is being developed, the folding off of the
embryo from the yolk-sac becomes more complete, and the
yolk-sac remains connected with the ileal region of the in-
testine by a narrow stalk, the vitelline duct. While the true
splanchnic stalk of the yolk-sac is becoming narrow, a somatic
stalk connecting the amnion with the walls of the embryo is
also formed, and closely envelops the stalk both of the
allantois and yolk-sac. The somatic stalk, together with its
contents, is known as the umbilical cord " (Balfour *). The
yolk-sac atrophies completely in some, but in others it is only
removed at birth.
1 Balfour, Comparative Embryology, London, 1881.
380 THE PHYSIOLOGY OF REPRODUCTION
II. THE NUTRITIVE IMPORTANCE OF THE YOLK-SAC
When the blastodermic vesicle becomes adherent to, or
sinks into, the uterine mucosa, the wall of the yolk-sac in some
orders becomes intimately related to the uterine mucosa and
is nourished by it. Even in the non-mammalian Vertebrata
the latter condition has been observed. In the Lacertilia
the yolk-sac absorbs nutriment from the uterus through the
porous shell. In Mustelus Icevis the embryos lie in a fluid
derived from the surface secretion and a lymphoid transudate
of the uterine mucosa. It passes through the porous shell to
reach the yolk-sac (Brinkmann J). In Seps chalcides, a reptile,
the insufficient supply of yolk is added to by a uterine secretion
containing degenerated cells and blood derivatives, the outer
layer of the blastocyst being distinctly phagocytic (Giacomini 2).
But in the Sauropsida no union takes place between the
maternal tissues and the foetal membranes, and so in one
order of Mammals, the Ornithodelphia,3 where the young de-
velop outside the body. In all the other orders the wall of the
yolk-sac comes into relation with the uterine wall over a greater
or less area, depending on the extent to which the mesoblast,
spreading round the wall of the blastocyst, splits into two layers.
In the non-mammalian Vertebrates, the mesoblast and the
coslom extend completely round and the yolk-sac is entirely
separated from the surface layer ; so in the sheep and Man.
In others (e.g. the rabbit) the ccelom does not spread so far.
It still remains to consider the path by which the nutriment
is conveyed to the embryo. In partial extension of the area
vasculosa, the wall of the yolk-sac consists of three parts, each4
with different relations (see Fig. 77) : — (1) The non- vascular part,
with a two-layered wall of epiblast and hypoblast ; (2) the
vascular part, where the mesoblast is unsplit, e.g. in the opossum
— the mesoblast splits in its entire extent in the rabbit ; (3) the
part opposite the ccelom. In all three parts the trophoblast is
1 Brinkmann, " Histologie, Histogenese und Bedeutung der Mucosa Uteri
einiger Viviparer Haie und Kochen," Mitt. a. d. Zool. Stat. z. Neapel.,
vol. xvi., 1903.
2 Giacomini, " Ueber die Entwicklung von Seps Chalcides," Anat. Anz.t
vol. vi., 1891.
3 Or Monotremata.
FGETAL NUTRITION: THE PLACENTA 381
bathed by the uterine secretion after the disappearance of the
prochorion. In the non- vascular part it is probably trans-
mitted through the hypoblast cells to the yolk-sac, whence, in
turn, it reaches the embryo either by the vitelline vessels or the
developing alimentary canal. In the vascular part the same"
may occur, or the nutriment may be conveyed to the embryo
directly by the vessels of the area vasculosa. It is in this region
that the foetal circulation is brought close to the maternal, and
gaseous exchanges may be effected. Opposite the ccelom
.M
FIG. 77. — Diagram to illustrate the three parts of the wall of the yolk-sac
in the rabbit. (From Minot's Human Embryology, by permission of
William Wood & Co.)
AL, allantois ; ApL, area placentalis ; EC., ectoderm ; Mes., mesoderm ;
Ent., extra-embryonic entoderm ; Cos., crelom ; En., entodermic cavity
of the embryo; Pro. A, proamnion.
the trophoblast is lined by a thin layer of non- vascular somato-
pleur, through which transference of material to the ccelomic
cavity is possible. This part is subsequently connected with
the embryo by the allantoic vessels. When the yolk-sac is
entirely separated from the outer wall, nutritive substances
may also be transmitted to the coelomic cavity and then to the
embryo or yolk-sac.
The nutritive importance of the yolk-sac may now be con-
sidered in greater detail in several orders of Mammals.
MARSUPIALS. — In the opossum the mesoblast spreads about
half-way round the wall of the blastocyst, but it does not split
382 THE PHYSIOLOGY OF REPRODUCTION
over its whole extent. Hence the ccelom is small, and corre-
spondingly the separation of the yolk-sac and trophoblast is
insignificant (Fig. 78). The allantois grows out into the
coelom only to impinge on and invaginate the wall of the yolk-
sac. It never comes in contact with the outer wall of the
blastocyst. The part of the wall where the mesoblast is unsplit
is thrown into folds which fit into corresponding furrows of the
mucosa. Hence an avillous yolk-sac placenta is formed
(Selenka 1). The nutrition in the uterus is very primitive.
EC mes
-Am \ /
s*
Cho
-Pro. am
Ent
FIG. 78. — Diagram of an opossum embryo and its appendages. (From Minot.)
All, allantois ; YJc, cavity of yolk-sac ; Cce, coelom ; Am, amnion ; Pro.am,
pro-amnion ; Emb, embryo ; EC, ectoderm ; Ent, entoderm ; mes,
mesoderm ; s.t, sinus terminalis ; Cho, chorion (diplo-trophoblast).
The ova contain a comparatively large supply of yolk granules
for the initial stages of development. As they travel along
the oviduct and into the uterus, they are invested with a thick
nutritive layer, derived from the secretion of the tubal and
uterine glands. Later the embryos are also nourished by the
primitive placental structures for a period short in duration,
but long enough to allow of the differentiation of their main
organs and systems. In the mucosa the surface epithelium
remains intact. The only change is an oedema of the layers,
and the sole nutritive material is a watery fluid, composed of
1 Selenka, Studien iiber die Entwicklungsgeschichte der Thiere, Wiesbaden.
FCETAL NUTRITION: THE PLACENTA 383
glandular secretion and a lymph transudate almost devoid of
cells. It is absorbed by the trophoblast cells, which here and
there enlarge to enormous " Nahrzellen " and so increase the
absorbing surface. After eight days the food supply becomes
inadequate for the developing embryos, and they are transferred
to the pouch and nourished by the mammary secretion.
bit omph.
proa I
vascomph.
amn.
-yspi
ch
FIG. 79. — Diagram showing the arrangement of the foetal membranes in
Dasyurus. (From Hill, "On the Foetal Membranes, Placentation and
Parturition of the Native Cat (Dasyurus viverrinus)," Anat. Anzeig.,
vol. xviii., 1900.
amn., trunk amnion ; all, allantois ; bil.omph, bilaminar omphalopleur ;
ch, chorion (diplo-trophoblast) ; coe, extra-embryonic splanchnocele ;
proa, proamnion ; proa.l, posterior limit of proamnion ; s.t, sinus ter-
minalis ; vasc.omph. vascular omphalopleur ; y.c, cavity of yolk-sac ; y.s,
yolk-stalk; yspl, invaginated yolk-sac splanchnopleur : the ectoderm is
represented by a thin line, the entoderm by a dotted line, and the
mesoderm by a thick line.
In Dasyurus the allantois is vascular over a small area and
comes in contact with the diplo-trophoblast (Fig. 79). But the
allantoic vessels degenerate rapidly and completely, and the
allantois again lies free in the coelom. In the region of the area
vasculosa the wall of the yolk-sac adheres to the uterine
epithelium, and, as in the opossum, forms a simple yolk-sac
384 THE PHYSIOLOGY OF REPRODUCTION
placenta. The superficial capillaries of the mucosa, which are
slightly dilated, are separated from the vitelline vessels by the
uterine epithelium and a thin layer of foetal ectoderm. Through
the two layers the gaseous exchange probably takes place.
Beyond the sinus terminalis, the non-vascular part of the wall
unites over an annular zone with the uterine epithelium by
enlarged ectodermal cells. These syncytial " Nahrzellen " are
phagocytic, and enclose fragments of epithelium and superficial
capillaries. Maternal blood is effused and lies in a space between
the ectoderm and entoderm, whence it is transmitted to the
cavity of the yolk-sac and serves for nutriment (Hill 1). The
gestation period is about eight days, as in the opossum.
In Perameles the placental structures are better developed
(Hill 2). Before the attachment of the blastocyst, the uterine
mucosa undergoes preliminary changes. The capillaries in-
crease in size and new vessels are formed ; the interglandular
tissue is composed of a loose network of anastomosing cells
and the inter-spaces are filled with lymph, the glands increase
in length and diameter, and the cells of the surface epithelium
lose their boundaries, and fuse to form a syncytium analogous
to the symplasma of higher forms (see p. 414).
Opposite the ccelom, the blastocyst becomes attached to a
discoidal area of the uterine symplasma by means of enlarged
ectodermal cells, and later its wall is vascularised by the allantois.
Outside the disc, the part corresponding to the area vasculosa
is also attached by an annular zone, and a yolk-sac placenta is
formed. The non-vascular part of the wall is bathed by the
uterine fluid as in the opossum (Fig. 80).
In the discoid area a functional allantoic placenta is de-
veloped. The ectodermal giant-cells, like the early tropho-
blastic proliferation in Man, disappear, and the allantoic vessels
become firmly attached to the symplasma into which the
maternal vessels penetrate. A regular interlocking of maternal
and foetal tissues is produced, and the two systems of blood-
vessels are separated at the most by a thin layer of symplasma.
1 Hill, "On the Foetal Membranes, &c., of the Native Cat (Dasyurus
viverrimis)," Anat. Anz., vol. xviii., 1900.
2 Hill, "The Placenta! ion of Perameles," Quar. Jour. Micr. Sci., vol. xl.,
1898.
METAL NUTRITION: THE PLACENTA 385
It is not yet determined whether the yolk-sac placenta is
functional till birth. According to Hill the wall probably breaks
up before the end of pregnancy. The allantoic placenta, on
the other hand, remains active, and at the time of birth some
amn
coe
vase,
ompfi
bil omph, yspl.
FIG. 80. — Diagram showing arrangement of foetal membranes in Perameles.
(From Hill, "The Placentation of Perameles," Quar. Jour. Micr. Sci.,
vol xl., 1897.)
amn, amnion ; all.c, allantoic cavity ; all.mes, allanto-chorionic mesenchyme ;
all.s, allantoic stalk; bilomph, bilaminar omphalopleur ; ch., marginal
zone of true chorion around the allanto-chorionic area ; coe, extra-
embryonic coelom ; coe.w, inner or chorionic wall of allantois ; proa.r,
persistent remnant of proamnion ; st, sinus terminalis ; vasc.omph,
vascular omphalopleur ; y.c, yolk-sac cavity ; y.spl., invaginated yolk-
sac splanchnopleur ; ectoderm represented by thin line, mesoderm by
dotted line, entoderm by thick line.
maternal tissue is shed, while part of the foetal tissue is left
behind. The gestation period is about eight days.
The allantois in Perameles is of greater importance than in
the opossum or Dasyurus ; but, relatively to the yolk-sac, it
plays a small part in the nutrition of the embryo, as evidenced
2s
386 THE PHYSIOLOGY OF REPRODUCTION
by the fact that the vitelline vein is thrice as large as the
allantoic vein.
UNGULATA.- — In the sheep the blastocyst elongates early, and
contains at one part the thickened embryonic area or shield
(Fig. 81). From it the mesoderm reaches out on all sides. As
it spreads between the epiblast and hypoblast, the coelom is de-
veloped in it. By the thirteenth day one-third of the circum-
ference is surrounded by ccelom, and in this area the yolk-sac
is separated from the outer wall. At the seventeenth day the
separation of the yolk-sac is complete all round (Bonnet 1).
It continues, however, to grow pari passu with the blastodermic
vesicle, and is gradually pushed to one side by the enlargement
FIG. 81. — Elongated blastocyst, of sheep at thirteenth day of pregnancy.
(From Hertwig's Entwicklungsgeschichte des Menschen und der
Wirbelthiere, by permission of Gustav Fischer.)
bl, blastocyst ; E, embryonic shield.
of the ccelom. At the twenty-fifth day it is reduced to a solid
rod of cells with a few blood-vessels on its outer surface (Fig. 82),
and it disappears before the end of pregnancy (Assheton 2). The
allantois grows out into the ccelom very early and expands
with extraordinary rapidity, occupying most of the cavity of
the blastodermic vesicle. Its further developments are de-
scribed later (p. 397). Hence in the sheep, and in the pig and
cow, in which the conditions are similar, the yolk-sac is func-
tional only from the first appearance of the vessels in the area
vasculosa till about the twentieth day of pregnancy.
CARNIVORA. — The mesoblast and ccelom extend completely
round the blastocyst, and the vitelline circulation is active
1 Bonnet, " Beitrage zur Embryologie der Wiederkauer," Arch. f. Anat.
u. PhysioL, 1889.
2 Assheton, "The Morphology of the Ungulate Placenta," Phil. Trans.
Roy. Soc., London, Ser. B., vol. cxcviii., 1906.
FCETAL NUTRITION: THE PLACENTA 387
Tr
AS
only in the early stages. In the dog the yolk-sac is large and
extends at first to the end of the citron-shaped ovum (Fig. 97).
According to Bischoff l it persists till birth, but this is denied
by Duval.2 The allantois grows out
on the dorsal side of the embryo,
and fuses with the diplo-trophoblast
over a small discoidal area. Later,
as the cavity of the allantois en-
larges, it adheres to the whole of
the blastocyst wall except the
poles. Subsequently the zone of
adhesion is reduced in extent (see
p. 413).
PROBOSCIDEA and HYRAX. —
The elephant and the aberrant
genus Hyrax have at full-time, like
the Carnivores, a zonary placenta,
but little is known regarding the
development of the foetal mem-
branes. Assheton 3 has recently
given an account of two early
embryos of Hyrax. In the younger,
the yolk-sac occupied about three-
quarters of the surface of the
blastocyst, and the allantois the
82 — Transverse section
through the blastocyst of the
sheep at the twenty-fifth day.
(From Assheton, "The Mor-
phology of the Ungulate
Placenta," Phil. Trans. Roy,
Soc., London, Ser. B., vol.
cxcviii., 1906.)
toic blood-vessel ; C, ccelom ;
V, commencing folds from
which villi spring ; Y, solid
yolk-sac.
remaining quarter, the ovum pos-
sibly being wholly embedded in A- allantois; AS, .splanchno-
* J pleur of allantois ; A.V, allan-
the uterine mucosa. The yolk-sac
was covered with a network of
vessels, and the head of the
embryo dipped into it. It was
invested externally with a mass of trophoblastic cells, honey-
combed with spaces and filled with maternal blood, but. no
villi were developed. In the second embryo the yolk-sac was
1 BischofF, Entwickelungsgeschichte der Sdugethiere und des Menschen,
1842.
2 Duval, "Le Placenta des Carnassiers, " Jour, de VAnat. et de la Phys.,
1893. 3 Assheton, Phil. Trans. Roy. Soc., London, loc. cit.
388 THE PHYSIOLOGY OF REPRODUCTION
much reduced, and was " presumably enveloped by the allantois."
It had previously been shown by Turner that the yolk-sac disap-
peared at an early period.
RODENTIA. — In Rodents the conditions are entirely different.
The mesoblast never extends, in the rabbit, rat, or mouse,
completely round the ovum, and the yolk-sac hypoblast remains
long in contact with the trophoblast, and carries on the nutrition
of the embryo till the tardily formed allantoic placenta is de-
veloped. Regarding the partial extension of the mesoblast,
Minot l says : " That it represents a modified condition is
Ent
EC
FIG. 83. — Blastodermic vesicle of the rabbit. (Minot.)
co?, coelom ; Cho, ch^orion (diplo-trophoblast) ; Yk, yolk-sac; mes, raesoderm ;
v t, vena terminalis ; Ent, entoderm ; EC, ectoderm.
evident, since in all non-mammalian Vertebrates both mesoderm
and coelom extend completely round the yolk. Hence the com-
plete separation of the yolk-sac in Man and the sheep is nearer
the ancestral type than the relations of the extra-embryonic
germ-layers to one another in the rabbit and opossum."
In the rabbit, the mesoblast begins to spread out from the
embryonic region about the end of the first week of gestation,
and it gradually reaches half-way round the circumference of the
blastocyst. It splits into two layers over its whole extent, and
it is limited below by the sinus terminalis (Fig. 83). The lower
half of the yolk-sac is non- vascular, and its wall of hypoblast is
closely invested by trophoblast. Later the yolk-sac begins to
1 Minot, Human Embryology, Boston, 1892.
FCETAL NUTRITION: THE PLACENTA 389
shrink, taking a mushroom shape, and its vascular half comes
against the non- vascular half (Fig. 84). The specially large
coelomic space, thus left by the shrinking of the vesicle, is filled
with fluid through which the allantois extends to reach the
part of the wall not covered by the yolk-sac. Hence at this
stage the whole wall of the blastocyst is vascularised, one half
by the vitelline and the other half by the allantoic vessels.1
From an investigation of the early stages in the mouse and
FIG. 84 — Diagram of the blastodermic vesicle of the rabbit in longitudinal
section. (From Hertwig's Entwicklungsgeschichte des Menschen und
der Wirbelthiere.)
e, embryo ; a, amnion ; a?, allantois with blood-vessels ; fd, vascular layer of
mushroom-shaped yolk-sac ; d.s, cavity of yolk-sac ; s.t, sinus terminalis ;
r, large space filled with fluid.
rat, Robinson 2 attaches much importance to the yolk-sac in
providing for the nutrition of the embryo. On the seventh day
the yolk-sac is large, and becomes invaginated with the inver-
sion of the germinal layers (see p. 438). Outside its thin wall
lies extravasated maternal blood, which is absorbed into the
cavity. Over a large area, the wall of the yolk-sac becomes
villous with a covering of columnar hypoblast. Over a small
1 Hertwig, Entwicklungsgeschichte des Menschen und der Wirbelthiere,
1906.
2 Kobinson, " The Nutritive Importance of the Yolk-Sac," Jour, of Anat.
and Phys., vol. xxvi., 1892.
390 THE PHYSIOLOGY OF REPRODUCTION
area the trophoblast is thickened and maternal blood circulates
in its spaces. But the allantois has not yet come in contact
with it, and the blood " must serve only for the nutriment of
the trophoblast itself/' At the eleventh day the trophoblast is
vascularised by the allantoic vessels, by which the nutriment is
now transmitted as well as by the vitelline vessels in the yolk-
villi. Then the yolk-sac becomes less important. The circula-
tion in the decidua reflexa, which surrounds it, decreases and
ceases altogether on the sixteenth day, and the wall of the
yolk-sac becomes thin and bloodless. " At the same time
numerous diverticula grow out from the entodermal sinus into
the hilum of the allantoic placenta, and these may still absorb
nutriment though they are more probably excretory/' Later
the outer wall of the invaginated yolk-sac undergoes atrophy
and completely disappears. The remains of the yolk-sac cavity
are in this way bathed in the uterine fluids. At the same time
the villi of the inner wall increase in size and complexity, but
whether they absorb the fluids or are entirely excretory is
uncertain.
In the spiny mouse (Acomys caharinus), Assheton l found in
a well-advanced pregnancy that the yolk-sac was still extremely
vascular, and covered with a columnar-celled epithelium which
was much folded. The blood-vessels lay in the folds, and so
approached closely to the placenta. The yolk-sac was firmly
attached to the placenta over the peripheral area, but not so
closely as described above for the rat and common mouse. In
the spiny mouse the folds do not become involved in the
placental tissues.
INSECTIVORA. — In the hedgehog, the yolk-sac forms a
placenta which nourishes the embryo until the mesoblast splits
into two layers and the allantoic placenta is formed. At a
very early stage the epiblastic wall of the blastocyst has spaces
in which maternal blood appears. As the mesoblast spreads out
in a single layer, the area vasculosa develops, and its branches,
contained in mesoblastic warts and ridges, interlock with
the adjacent trophoblast to form yolk- villi (Fig. 85). The yolk-
1 Assheton, " On the Foetus and Placenta of the Spiny Mouse," Proc. Zool.
Soc., London, 1905, vol. ii.
FOETAL NUTRITION: THE PLACENTA 391
sac or omphaloidean placenta reaches its full development at
the time when the allantois comes in contact with the tropho-
blast (see p. 451). Then the yolk-sac is gradually separated
from the wall, more and more of its villi being peeled out from
the trophoblast as the separation increases. The vitelline
circulation at the same time diminishes, though it never ceases
entirely (Hubrecht 1).
Allantoidean region
fS of trophosphere
Omphaloidean
region of
trophosphere
Decidua reflexa
Uterine
lumen
^ _ . | Mesometrium
FIG. 85.— Diagram to illustrate the foetal membranes of Erinaceus. (From
Hubrecht's "The Placentation of Erinaceus europceus" Quar. Jour.
Micr. Sci., vol. xxx., 1889.)
In the shrew, the yolk-sac adheres by a zonary strip to
lateral cushions of proliferated mucosa, but the resulting yolk-
sac placenta is avillous (Hubrecht 2). The trophoblast is again
thickened, and in its spaces maternal blood appears, but at a
later date than in the hedgehog. The maternal blood is bodily
1 Hubrecht, " The Placentation of Erinaceus europceus" Quar. Jour.
Micr. Sci., vol. xxx., 1889.
2 Hubrecht, " The Placentation of the Shrew," Quar. Jour, Micr. Sci.,
vol. xxxv., 1894.
392 THE PHYSIOLOGY OF REPRODUCTION
absorbed, and at the same time the yolk-sac contains a charac-
teristic yellowish-green, glassy coagulum with granules in it.
Later the mucosal cushions disappear and the adjacent tropho-
blast thins (see p. 454).
In the mole a simple yolk-sac placenta persists throughout
pregnancy (Robinson l). Unlike the hedgehog and the shrew,
in which the gland lumina are plugged by the trophoblastic
syncytium, there is in the mole a copious glandular secretion
containing degenerated cells, which is absorbed by the tropho-
blast (see p. 456),
Tv.paia javanica differs from the other Insectivora in having
a temporary yolk-sac placenta formed in the same situation as
the allantoic placenta subsequently occupies (see p. 458). The
same occurs in the bat (p. 462).
PRIMATES. — In monkeys, old- and new-world, there is no
decidua reflexa, and a portion of the trophoblast is in contact
with the uterine fluids. But even in Selenka's earliest specimens
of monkeys and apes, the yolk-sac is a small, closed sac attached
to the ventral surface of the embryonic area, and is entirely
separated from the trophoblast. The embryonic area is con-
nected with the inner surface of the chorion by a short stalk of
mesoderm, in which the vessels run.
In the youngest human ovum yet examined, the yolk-sac is
also a small, closed vesicle, separated from the trophoblast by a
single thick layer of mesoblast (Fig. 86). The splitting of the
mesoblast occurs very early, even before the appearance of the
primitive streak, and the ccelom spreads round the whole circum-
ference of the ovum. The earliest vessels appear on the under
surface of the sac, and gradually extend over its upper pole,
until the whole sphere is covered by a vascular network. The
vessels are in direct continuity with vessels which develop in
the connecting-stalk (see p. 463), and through them with the
vessels of the chorion by a vascular loop, the sinus ensiformis of
Eternod (Bryce 2). This communication appears to exist before
any vessels appear in the embryo itself. From the third
week onwards, saccular dilatations of the entodermal lining of
1 Robinson, Hunterian Lect., loc. cit.
2 See Quairfs Anat., vol. i., Part I., 1908.
FCETAL NUTRITION: THE PLACENTA 393
the yolk-sac are produced, and from their walls solid masses of
cells are budded off, resembling liver-tissue in its simplest form
and perhaps functioning as such (von Spee *). The sac grows
up to the end of the fourth week. It is then pear-shaped, and
FIG. 86. — Hypothetical section of the human ovum embedded in the decidua,
somewhat younger than Peters' ovum. The trophoblast is greatly
thickened, and lined with mesoderm, which surrounds also the embryonic
rudiment, with its yolk-sac and amnio-embryonic cavity (T. H. Bryce
in Quain's Anatomy). The embryonic rudiment is proportionally on too
large a scale.
is united to the intestine by a long neck in which the cavity is
obliterated. The vesicle persists throughout pregnancy. Little
is known of its contents ; at the end of pregnancy it contains
variable quantities of fatty substances and carbonates
(Schultze 2).
1 See Quain's Anatomy, vol. i., Part I., 1908.
2 Schultze, " Ueber die Embryonalhiillen und die Placenta der Saugethiere
und des Menschen," Sitzungsb. d. Wurzburger physik.-med. GeselL, 1896.
394 THE PHYSIOLOGY OF REPRODUCTION
III. THE PLACENTA IN INDECIDUATA
In the placental Mammals, an attachment takes place be-
tween maternal and foetal tissues in the uterus, and the tropho-
blast is vascularised, except in the Primates, by the allantois.
The method of attachment varies in different orders, and
sometimes in different groups of an order. In the Indeciduata,
FIG. 87. — Portion of the injected chorion of the pig. The figure shows a
minute circular spot, 6, enclosed by a vascular ring from which villous
ridges (r, r) radiate (Turner). (From Balfour's Comparative Embryology,
vol. ii. By permission of Messrs. Macmillan & Co., Ltd.)
however, the first attachment is always obtained by an apposi-
tion of the trophoblast to the surface of the mucosa.
UNGULATA : Pig. — In the pig the blastocysts are spherical till
the tenth day. Then they rapidly elongate, and by the four-
teenth day they fill the whole length of the uterus. Subsequently
they obtain a greater surface of contact by a series of concer-
tina-like foldings (Assheton 1), which fit between ridges of the
uterine mucosa. The ridges are inter-glandular in position
1 Assheton, Phil. Trans., loc. cit.
FCETAL NUTRITION: THE PLACENTA 395
(Fig. 87), radiating from small circular spots, twenty or thirty
to the square inch, which represent the gland-mouths (Turner 1).
It is usually stated that the uterine surface epithelium remains
intact ; but Assheton has recently proved that it shows signs of
degeneration as early as the eighth day, and at the eighteenth
day is reduced to a thin layer. Three days later, however, it
again appears normal and is formed of long columnar cells, to
the ends of which the trophoblast fits closely, sending prote-
Tr
*-»
EP
FIG. 88. — Section through the wall of the uterus and the blastocyst of the
pig at the twentieth day of pregnancy (Assheton).
mes, mesoblast ; Bl.v, foetal vessel ; Tr, trophoblast ; Ep, long columnar
epithelium of uterine surface.
plasmic processes between the cells (Fig. 88). These processes
may even reach past the epithelium to the underlying layer
of dilated capillaries (Robinson), and absorb nutritive material
or effect gaseous exchanges.
The trophoblast is single-layered throughout, and, after the
first three weeks, forms a syncytium. Internally to it lies the
mesoblast, which in the main follows its ridges and furrows,
but occasionally bridges across a fold. It is vascularised by the
vessels of the allantois, which completely surrounds the embryo.
The gland-mouths lie along the course of the vessels (Assheton).
No formation of villi takes place, and the attachment never
1 Turner, Lectures on the Comparative Anatomy of the Placenta, Edinburgh,
1876.
396 THE PHYSIOLOGY OF REPRODUCTION
goes beyond the stage of apposition except for the proto-
plasmic extensions of the trophoblast (Fig. 89).
The uterine mucosa contains no special cotyledonary
areas such as are found in the sheep and cow. The surface
epithelium, though it shows the degenerative changes already
referred to, is apparently never completely destroyed. The
glandular epithelium does not at any time show signs of de-
generation. It secretes actively during the early stages, and
probably during the whole of pregnancy. As in the sheep and
one of the lemurs (Galago agisymbanus), the glandular orifices
MB
FIG. 89. — Diagram representing a stage in the formation of the placenta of
the pig. (From Kobinson, " Hunterian Lectures," Jour. Anat. and
Phys., vol. xxxviii., 1904.)
UM, uterine muscle ; MB, maternal blood-vessel ; UG, uterine glands ;
UE, uterine epithelium ; FE, foetal ectoderm ; FM, fcetal mesoderm.
are covered by domes of trophoblastic cells, which absorb the
secretion and transmit it as nutriment for the developing
embryo by the allantoic vessels. The sub-epithelial tissue is
gelatinous, and early in pregnancy it begins to increase in
thickness by a widening of the lymphatics and blood-vessels
and a new formation of capillaries. The constituents of the
nutriment provided for the embryos are referred to later (see
p. 400).
Mare. — In the mare the details of placental development are
not yet known. In the early stages the blastodermic vesicle
is attached to the uterine mucosa by the trophoblast covering
the lower pole of the ovum, and the attachment is aided by the
formation of delicate, nearly parallel ridges (Ewart l). Villi are
1 Ewart, Critical Period in the Development of the Horse, London, 1897.
POSTAL NUTRITION: THE PLACENTA 397
formed in the allantoic region, and they fit into crypts which
are probably lined with maternal epithelium. Between the
foetal and maternal tissues in the crypt is a space filled with
secretion. The lymphatic system of the mucosa is enormously
developed (Kolster 1).
Sheep. — In the sheep and cow the poly-cotyledonary type of
placenta is found. The form is determined by the presence
from an early period, and independently of pregnancy, of
numerous prominences or cotyledonary buns, which project as
thickened knobs of the sub-epithelial tissue into the uterine
lumen. During pregnancy they form connections with localised
proliferations of the trophoblast. The burrs vary in number
from fifty or sixty in the sheep to five or six in the roe-deer.
The ova of the sheep reach the uterus four or five days after
coitus, and the blastodermic vesicles remain free till the seven-
teenth day. Then the attachment to the mucosal surface
begins, and it is completed by the thirtieth day (Assheton).
After the ninth day, when the prochorion ruptures, the tropho-
blast comes in contact with the uterine epithelium. Apparently,
as the result of this, the absorption of nutriment is easier, and
the blastodermic vesicle increases rapidly in size so as to fill the
uterine horn, or both horns if only one embryo is present.
Certain changes occur in the mucosa before attachment.
The leucocytes, which in the non-pregnant uterus are situated
at the base of the lining epithelium, increase in number and
penetrate between the epithelial cells. The glandular sacs,
situated at the junction of the branches with the main ducts,
expand greatly and actively secrete. It is generally held that
the surface epithelium is not destroyed, but Assheton has shown
that on the cotyledonary burrs it is distinctly degenerated by
the seventeenth day, and he has also brought forward strong
evidence that it is not subsequently regenerated, but is re-
placed by binucleate cells of the foetal ectoderm.
In the cotyledonary areas of the trophoblast, villi are de-
veloped as buds of epiblast, which afterwards contain cores of
mesoblast with branches of the allantoic vessels (Fig. 90). They
1 Kolster, " Die Embryotrophe placentarer Sauger, mit besonderer Beriick-
sichtigung der Stute," Anat. Hefte, vol. xviii., 1902.
398 THE PHYSIOLOGY OF REPRODUCTION
fit into depressions or crypts on the surface of the cotyledons,
increase in length, and branch in different directions. Whether
they literally grow into the maternal tissues either mechanically
or by a phagocytic action is uncertain.1 It seems more likely
that very little, if any, further penetration occurs, but that the
sub-epithelial tissue swells and keeps pace with the villi as they
increase in length. The crypts, if their lining cells really belong
to the foetal ectoderm, are not secretory, and there is no free
space, such as is described in the mare, between them and the
villi. The sub-epithelial tissue is represented in the non-
FIG. 90. — Section through the uterine and embryonic parts of a cotyledon
of the sheep at the twentieth day of pregnancy. Folds in the tropho-
blast fitting into sulci of the cotyledonary burr. (Assheton.)
mes, mesoblast ; tr, trophoblast ; us, degenerated uterine epithelium ;
str, uterine stroma.
pregnant uterus by a thin layer of dense connective tissue,
with localised thickenings in the burrs. With the onset of
pregnancy occur an infiltration of lymph between the more
superficial cells of the sub-epithelial layer, and an increase in
the number and size of the blood-capillaries and lymphatics.
Thus the layer becomes spongy and swells up around the foetal
villi, producing the cotyledonary interdigitation. At the fundus
of the crypts the lining cells become syncytial. At the apices of
the inter-crypt columns lacunae of maternal blood are formed by
repeated small haemorrhages from the superficial capillaries
(Fig. 91).
1 At this stage Assheton did not observe any actual engulfment of cells,
but considered that nutriment might be transmitted by fine processes of the
binucleate cells which united with similar processes of the connective tissue
cells of the mucosa.
FCETAL NUTRITION: THE PLACENTA 399
In the inter-cotyledonary area, the epithelium, whether or
not it degenerates over large areas in the early stages as
Assheton supposes, is later healthy and vigorous. There is no
formation of a spongy layer in the sub-epithelial tissue as in
the burrs. But a great change occurs in the glands, which a:ne-
wholly inter-cotyledonary in position. They increase in length
and complexity, and secrete actively. Towards the end of
m.v Tr Ic.
FIG. 91. — Section through the base of a foetal villus and the apices of two
inter-crypt columns. Sheep. The surfaces of the columns are traversed
by large blood-vessels which later rupture and form the blood-extravasa-
tions. (Assheton.)
Tr, trophoblast dipping into crypt ; /c, inter-crypt column ; m.v, maternal
blood-vessel.
pregnancy, however, the greater part of the uterine glands is
destroyed, but the surface epithelium still secretes. At the
upper end of each horn the wall of the blastocyst forms a
crumpled structureless membrane with no trace of nuclei,
while the uterine mucosa in this region is thrown into folds and
covered with a high columnar epithelium which is very active.
The secretion is apparently transmitted by transfusion through
the membranous wall, and is found inside the sac. At full-
400 THE PHYSIOLOGY OF REPRODUCTION
time this part of the mucosa shows signs of great degenera-
tion , resembling the pulpe diffluente of Duval in the guinea-pig
(Assheton). The inter-glandular cells also hypertrophy like the
connective tissue cells of Rodents.
The inter-cotyledonary trophoblast is avillous in the sheep
and cow. In the giraffe, however, there are rows and clusters
of villi in addition to the cotyledonary villi.
The development and structure of the placenta of the sheep
have been described at some length because the formation of
the special nutriment for the foetus has received close atten-
tion in that animal.1
Cow. — In the cow (Fig. 92) the placenta has essentially the
same form as in the sheep, but the interlocking is not so firm.
On separation of the maternal and foetal parts of the cotyledons,
the former are found to comprise the larger part. In the
fully developed sheep's placenta the foetal parts constitute the
main mass of the cotyledon. The various stages of develop-
ment have not been completely investigated, but one other
difference has been noted, viz. the absence of lacunae of maternal
blood at the bases of the villi (Ledermann 2).
The Uterine Milk
The existence of a nutritive juice in the uterus of Ruminants
during pregnancy has been recognised since the days of Harvey.
He spoke of an albuminous fluid, which might be squeezed out
from the cotyledons of the placenta, as a source of nutriment
for the foetus. As to its origin, he says in one of his Letters :
" It might be transported by the uterine arteries and distilled
into the uterus." The fluid was first called uterine milk by
Needham in 1667. Haller described it as a secretion of the
utricular glands, and this view was supported by Bischoff,
Sharpey, and others, who considered it the immediate store of
1 For the above account of the development and structure of the sheep's
placenta, we are largely indebted to the important memoir of Assheton.
Differing in many respects from previous descriptions, it alone brings forward
evidence that the Ungulate placenta may be " secondarily simplified " in
Hubrecht's sense (see Quar. Jour. Micr. Sci., 1908).
2 Ledermann, " Ueber den Bau der Cotyledonen im Uterus von Bos," &c.
Inaug.-Diss., Berlin, 1903.
FCETAL NUTRITION: THE PLACENTA 401
foetal nutriment. It was analysed by Gamgee,1 who showed
that the fluid contained a large amount of protein and fat and
some salts, and was thus well adapted for nutrition.
But Haller's view of its origin was not accepted by Turner 2
and Ercolani.3 Turner showed that during pregnancy new"
crypts were formed in the cotyledons, and he supposed that
FIG. 92.— Columnar trophoblast-cells from the base of a fcetal villas of the
placenta of the cow at the third month of pregnancy, to show phago-
cytosis. (From Jenkinson's " Notes on the Histology and Physiology
of the Placenta in Ungulata," Proc. ZooL Soc. , London, vol. i., 1906.)
the uterine milk represented the secretion of these crypts.
Ercolani went even further and stated that such a secretion
existed in ah1 placentae, but Turner was strongly opposed to
this : ''' That such a fluid (uterine milk) is produced in all
placentae, where utricular glands or follicles continue to secrete
during the whole period of placental formation, is very probable.
1 Gamgee, "On the Chemistry and Physiology of the Milky Fluid found
in the Placental Cotyledons of Ruminants," Brit, and For. Med.-Chir.
Review, 1864.
2 Turner, "The Placentation of the Sloths," Jour, of Anat. and Phys.,
vol. viii., 1874.
3 Ercolani, " Sull' unita del tipo anatomico della placenta," Mem. dell1
Accad. di Bologna, 1876.
2c
402 THE PHYSIOLOGY OF REPRODUCTION
But in the placentae of the sloth, the apes, and the human
female, where an unusual development of the maternal blood-
vessels into larger sinuses takes place, a modification in the
anatomical structure is produced which seems to render the
presence of such a secretion unnecessary. The nutritive changes
in all probability take place directly between the maternal and
fcetal blood/'
More recent investigations have thrown fresh light on the
origin, composition, and absorption of uterine milk. It must
be recognised that, even before the onset of pregnancy, changes
occur in the uterus which are important for the nourishment
of an embryo developing later. Shortly before the first cestrous
period, the mucosa " matures " by the formation of the richly
cellular sub-epithelial layer of connective tissue already re-
ferred to (see p. 398). Among Indeciduates it is specially well
marked in the cotyledonary types. With the first procestrum
the mucous membrane becomes oedematous, and the super-
ficial capillaries are dilated. Many of them rupture and give
rise to miliary haemorrhages, which later undergo changes such
as occur in haemorrhages elsewhere. Whether the changes are
caused by an enzyme action on the part of the leucocytes is
uncertain ; but in any case the white corpuscles take up the
pigmented products of disintegration, and then arrange them-
selves in a row, or in groups, close under the surface epithelium
in the manner described in an earlier chapter (Chap. III. p. 109).
Some of the leucocytes contain unaltered haemoglobin, as is
shown by the characteristic reaction with eosin ; others contain
derivatives of it, in which iron may often be demonstrated.
With the onset of pregnancy these cells wander out between the
epithelial cells, and mingle with the secretion lying in the uterine
cavity. This secretion is poured out by the superficial and
glandular epithelium, which becomes more active at the be-
ginning of pregnancy with the increased flow of blood and
lymph through the mucosa. It forms the more fluid part of
the uterine milk in which the formed constituents lie. It is
necessarily found only in the extra cotyledonary regions since
no glands exist in the burrs.
Besides the intracellular pigments, there is another source
of iron, though in widely varying amounts. In all placental
FCETAL NUTRITION: THE PLACENTA 403
Mammals a greater or less amount of maternal blood is in direct
contact with the trophoblast. In the pig and mare it is re-
stricted to individual red blood corpuscles, which find their way
to the surface and mingle with the gland secretion. In the ass_
Strahl l has found blood in greater amount, forming small
effusions. In the sheep its presence has often been noted by
Tafani,2 Bonnet,3 and others. The position of the extravasa-
tions in the placenta has been already referred to (see p. 398).
In the cow they are apparently not a constant phenomenon,
the supply being often restricted, as in the mare, to a few single
erythrocytes. In the deer, blood is effused into the glands,
but no extravasations take place in the cotyledons. Here the
whole of the maternal part of the burr appears to be digested
and absorbed by the trophoblast. The greater activity of the
foetal ectoderm in the deer is also shown by the destruction
of the epithelium over the whole surface of the uterus (Strahl 4).
In addition to blood, the uterine milk contains fat in large
quantities. Before pregnancy it may be demonstrated in the
sub-epithelial leucocytes which later migrate to the surface.
Fat globules are also contained in large amount in the epithelial
cells of the surface and glands. According to Bonnet, it cannot
be considered as a fatty degeneration because the cells are
otherwise healthy ; it is rather a fatty infiltration, the epithelium
secreting it from the lymph or blood-plasma, storing it and later
giving it off to the uterine milk.
Kolster 5 has described a process by means of which cellular
elements are added to the " Embryotrophe." 6 The gland
1 Strahl, see Hertwig's Handb. d. vergl. u. exp. Entwickelungsg. d.
Wirbelthiere, 1902.
2 Tafani, " Sulle Condizioni utero-placentari della Vita Fetale," Arch,
della Scuala d'Anat.-Path., Firenze, 1886.
3 Bonnet, "Ueber Embryotrophe," Deut. Med. Woch., 1899.
4 Strahl, " Ueber die Semiplacenta multiplex von Cervus elaphus " Anat.
Hefte, H. xciii., 1906.
5 Kolster, "Die Embryotrophe placentarer Sauger," &c., Anat. Hefte,
vols. xviii. and xix., 1902 and 1903.
6 Objections have been raised to the term " uterine milk " because the
fluid contains cellular elements, pigment granules, &c., which are not present
in the mammary secretion. Bonnet and his followers have employed the
convenient term "Embryotrophe," but it must be noted that in the sheep
it forms the nutriment long after the embryonic stage of the developing
ovum is past. The two terms are used indiscriminately in this chapter.
404 THE PHYSIOLOGY OF REPRODUCTION
epithelium proliferates so strongly that the cells cannot find
room in the wall, and tracts of them are invaginated into the
lumen. Later the cellular projections, sometimes along with
some of the underlying connective tissue as in the mare, are
cut off and added to the embryo trophe (Fig. 93).
Traces of glycogen may be extracted from both the maternal
and foetal parts of the cotyledons, but it is too small in amount
to be demonstrated histologically. It is also present in small
amounts in the extra-cotyledonary areas — in the uterine
epithelium both superficial and glandular in the cow, in the
sub-epithelial connective tissue in the sheep, and in the uterine
milk (Jenkinson 1). Large quantities of glycogen are stored in
the plaques amniotiques, localised masses of cells on the internal
surface of the amnion, and later on the umbilical cord. In the
calf embryo the plaques reach their full development about the
sixth month, and then gradually atrophy.
It is obvious that the uterine milk must contain many
elements which have not been mentioned individually. The
product of conception requires numerous other substances
for its development besides protein, fat, carbohydrate, and iron.
Organic phosphorus compounds are furnished by the nuclei of
cells, and these may also contain iron. In general the fixation
of mineral elements is slight at the beginning of pregnancy,
but becomes active towards the end. But the requirements
vary at different periods of pregnancy. For example, sodium
decreases and calcium increases with the replacement of cartilage
by bone, and potassium increases with the increased manu-
facture of red blood corpuscles. These and many other sub-
stances are present in uterine milk though not demonstrated
histologically. Either they have been dissolved by the fixative,
or have remained unstained by the methods hitherto employed.
One other constituent has been described by various ob-
servers, but its composition and significance are unknown.
Besides the leucocytes that contain pigment granules and fat,
others are filled with rod-like bodies, the " Uterinstabchen " of
Bonnet.2 Later they appear in the uterine milk. Rods have
1 Jenkinson, " Notes on the Histology and Physiology of the Placenta
in Vertebrata," Proc. Zool. Soc., London, 1906, vol. i.
2 Bonnet, " Beitrage zur Embryologie der Wiederkauer gewonnen am
Schafe," Arch. f. anat. u. Phys.t anat. Abth., 1884.
FCETAL NUTRITION: THE PLACENTA 405
also been described in the trophoblast of the rabbit by
Beneden, and in the uterine mucosa by Schmidt,1 who stated
&•£*
0 *<il/& i
FIG. 93. — First stage of cellular secretion in the placenta of the cow.
Invagination of glandular epithelium and some of the underlying con-
nective tissue. (From Kolster, " Die Embryotrophe placentarer Sauger,"
Annt. Hefte, vols. xviii. and xix., 1902-3.)
that they were composed of calcium oxalate. In Ruminants
they are found in enormous numbers, but whether they form
1 Quoted by Bonnet, " Ueber Embryotrophe," Munch, med. Woch., 1899.
406 THE PHYSIOLOGY OF REPRODUCTION
a supply of calcium for the foetus is not known (Fig. 95).
There is at present no evidence that they are " protein
crystals/' a name sometimes applied to them.
The uterine milk has thus the following constituents — the
secretion of the superficial and glandular epithelium, perhaps
mingled with lymph transuded from the oedematous mucosa ;
leucocytes containing haemoglobin derivatives, fat globules, and
" Stabchen " ; glycogen ; tracts of glandular epithelium set free
by a process of " cellular secretion " ; red blood corpuscles and
their derivatives ; connective-tissue elements ; salts, &c., which
are in solution and not recognisable by ordinary histological
methods.
While lying free in the uterine cavity, the uterine milk under-
goes changes which consist largely in a disintegration of its
cellular elements. The leucocytes degenerate and their cyto-
plasm, with the pigment granules, fat globules, and " Stabchen/'
is set free. The tracts of glandular epithelium are also trans-
formed into a mass of debris, and their contents lie free in the
embryo trophe. The red blood corpuscles may be ingested
almost unaltered by the trophoblast, or they may first be laked,
and the haemoglobin may be absorbed as such, or undergo
changes before absorption. According to Jenkinson, haemo-
globin is broken up into an iron-containing and an iron-free part.
The former is carried away by the foetal blood-vessels and
stored in large quantities, principally in the foetal liver, as a re-
serve for use during lactation. The iron-free part is deposited
in the cells as a pigment, occurring in such amount as to give,
especially in the later stages of pregnancy, a deep brown colour
to the foetal cotyledons. It collects at the apices of the villi,
and its presence suggests that the cotyledons are actively en-
gaged in excretion (Assheton). The histological changes in the
red blood corpuscles absorbed by the trophoblast have been
described by Jenkinson. They are engulfed by amoeboid pro-
cesses of the cells, and gradually become paler in colour and
irregular in outline ; often they clump together. Gradually
yellowish-brown granules are deposited on the surface of the
included cells, and this process continues till the whole is con-
verted into a dark brown mass. Bonnet called the granules
hsematoidin crystals, but Jenkinson was unable to demonstrate
FOETAL NUTRITION: THE PLACENTA 407
this pigment in alcoholic extracts of the placenta. He found
two other pigments, one absorbing a small part of the violet end
of the spectrum, and the other showing two absorption bands,
which differed slightly from those of oxyhsemoglobin in neutral
solution and of ha3matoporphyrin in acid solution. This pig
ment is obviously a hemoglobin derivative, and from it bilirubin
may be formed. It is present in the sheep and cow during
pregnancy, but not in the virgin uterus of the sheep. A similar
yellowish-brown pigment occurs in the crypts and the tissues
outside them, and also, according to Assheton, in the maternal
blood-stream. It is not yet possible to explain the exact
significance of these changes. The iron-free pigment is appa-
rently a waste product, and the iron-containing part is stored in
the foetal organs. Whether the foetus subsequently synthesises
part of the organic iron compound into hemoglobin, or absorbs
minute quantities of haemoglobin as such, according to its re-
quirements, is unknown.
The cotyledonary and inter-cotyledonary parts of the placenta
present differences both anatomically and physiologically. In
the inter-cotyledonary region are the glands, and here only are
found the gland-secretion and the " cellular " secretion. In
the cotyledonary parts the glands are absent. Here the villi
are formed, and they effect an attachment to the mucosa by the
greater activity of the trophoblast. Assheton has suggested
that this hyper-activity may be stimulated by the absence of
glands and consequently of uterine milk in the cotyledons, the
foetal ectoderm attacking the mucous membrane more vigorously
in order to obtain food. The blood effusions are also cotyle-
donary, and the eosin and iron reactions are obtainable in the
adjacent trophoblast, and not at other places. Finally, it is
probable that the exchange of oxygen and carbonic dioxide is
carried out in the cotyledons. Here the maternal capillaries
are more dilated than outside the burrs, and they come close
up to the surface, some of them even impinging on the lining
membrane of the crypts. Between them and the allantoic
vessels in the villi intervene only a small amount of mesoblast,
the cellular trophoblast, and the lining of the crypts which,
according to Assheton, corresponds to the plasmodiblast of the
bat. In the inter-cotyledonary regions, on the other hand, the
408 THE PHYSIOLOGY OF REPRODUCTION
foetal vessels are related to the orifices of the glands, and appear
to be concerned principally with the absorption of their secre-
tion. As already mentioned, the villi may also be concerned
with the excretion of waste products of hemoglobin.
Bonnet was the first to show that the trophoblast in
Ruminants was actively phagocytic and absorbed the consti-
tuents of the uterine milk (Fig. 94). He demonstrated the
presence of fat-globules, haemoglobin and its derivatives, de-
generated leucocytes and " Stabchen "
(Fig. 95) — in short, all the histologi-
cally demonstrable constituents of the
embryotrophe — in the trophoblast.
Many, if not all, of the cellular ele-
ments are partially degenerated before
absorption. The appearances suggest
an enzyme action on the part of the
trophoblast, and perhaps also the
FIG. 94.— Ingestion and dis- leucocytes, but no proteolytic or
integration of red blood iipOiytic enzyme is contained in
corpuscles by the tropho- • • f i
blast of the sheep. (From gljcerm extracts of the maternal
Jenkinson's " Notes on the or foetal part of the cotyledon.
After their absorption, the disin-
Histology and Physiology
of the Placenta in Ungu-
lata," Proc. Zool. Soc.,
I the Placenta in Cngu- tegration of the cellukr constituents
London, vol. i., 1906.) is completed in the trophoblast, and
they are no longer recognisable as
individual elements. Their products are transmitted to the
fcetal vessels, though they may first be elaborated in the
trophoblast into a form or forms suitable for the use of
the embryo in the development of its various organs.
LEMUROIDEA. — Many of the lemurs have a simple avillous
diffuse placenta, as Turner * first pointed out in specimens
from Madagascar. Hubrecht has investigated two others found
in the East Indies — Tarsius 2 and Nycticebus* The latter has
also a diffuse placenta. Villi develop over the whole of the
1 Turner, "On the Placentation of the Lemurs," Phil. Trans. Roy. Soc.,
London, vol. clxvi., 1876.
2 Hubrecht, "Ueber die Entwicklung des Placenta von Tarsius," &c.,
Internat. Congr. of Zool., Cambridge, 1898.
3 Hubrecht, " Spolia Nemoris," Quar. Jour. Micr. Sci., vol. xxxvi., 1895.
FCETAL NUTRITION: THE PLACENTA 409
chorion, and fit into vascular crypts in the uterine mucosa
from which they are easily retracted at birth. The epithelium
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of the crypts persists as in the cow, and the " osmotic inter-
change takes place through two cell-layers of different origin,
and of different physiological significance (phylogenetically).
410 THE PHYSIOLOGY OF REPRODUCTION
Tarsius approaches more closely to the Insectivora and Primates*.
The trophoblast proliferates and penetrates into the mucosa,
and maternal blood circulates in its spaces. The mesoblast
grows profusely, and forms with the trophoblast a true chorion
in Hubrecht's restricted sense. The placenta is discoid. In
Galago agisymbanus, Strahl 1 has shown that a layer of secretion
lies between the uterus and the ovum from the beginning of
pregnancy. It is absorbed by the ectoderm, the cells of which
are vesiculated over the gland orifices. Many blood extravasa-
tions occur in the connective tissue of the mucosa, and the red
blood corpuscles undergo changes as in the sheep, the glandular
cells and embryotrophe containing granules which give an iron
reaction. Turner 2 had previously noted in lemurs, the intense
brown staining of the glands from effused blood.
CETACEA, EDENTATA, and SIRENIA. — The details of placental
development and the constitution of the embryotrophe are
unknown.
IV. THE PLACENTA IN DECIDTJATA
In the Deciduata three modes of attachment between embryo
and mother are found : Centric, in which the blastocyst rests in
the cavity of the uterus, attains a large size, and comes in con-
tact with the wall over its whole circumference ; Excentric, in
which the blastocyst remains small and lodges in a furrow of
the uterine mucosa, and later a decidua reflexa is formed ;
Interstitial, in which the small blastocyst attacks the mucosa
at one point and reaches the connective tissue. In this form
also a decidua reflexa is formed.
In the neighbourhood of the attachment the mucosa de-
generates, but the connective tissue cells usually enlarge to
form decidual cells before degeneration sets in. The capillaries
dilate and come in contact with the trophoblast. The mucosa
interlocks so closely with the foetal villi that the two tissues
cannot be separated without injury.
1 Strahl, " Die Verarbeitung von Blutextravasaten dutch Uterindriisen,"
Anat. Anzeig., vol. xvi., 1899.
2 Turner, " The Placentation of Lemurs," Jour, of Anat. and Phys.,
vol. xii., 1878.
FCETAL NUTRITION: THE PLACENTA 411
CAENIVORA. — The Carnivora are characterised by a zonary
form of deciduate placenta. The following account of its
development refers particularly to the dog and cat, which have
been most frequently investigated. The gestation period in
the cat is about sixty-three days, and in the dog fifty-eight~to~
sixty-two days. In both the ovum takes a comparatively long
time to traverse the oviduct. On reaching the uterus the
blastocyst is covered by a thick prochorion which prevents
adhesion for a considerable period.
The mucosa is matured, as in Ungulates, at the first pro-
oestrum by the development of a well-differentiated sub-
epithelial cellular layer, and of the glands and crypts (see p. 398).
The crypts provide an increase of superficies and of secreting
epithelium, and are later concerned in the attachment of the
ovum. They have been recognised by all the authorities with
the exception of Robinson,1 who states that he can find no
evidence that any of the crypts are other than the ducts of the
uterine glands. At the first and each succeeding procestrum
there is a marked hypersemia of the mucosa, and from the
rupture of some of the superficial capillaries miliary haemorrhages
occur (see Chap. III.).
At the beginning of pregnancy, blood effusions are found
close under the surface of the mucous membrane, but bleeding
into the uterine cavity, which took place during the procestrum,
has entirely ceased. The epithelium of the surface glands and
crypts is swollen and pervaded with minute fat-globules in the
dog (Bonnet 2) and cat (Melissenos 3). The glands widen
quickly into " chambers/' and tracts of their proliferated
epithelium are invaginated, and often obliterate the lumen.
The widening of the glands and crypts makes the deep layer
spongy. The capillaries increase and form practically the
whole of the sub-epithelial layer. Immediately below it lies
the layer of glandular ducts which are obliterated by debris
1 Robinson, Hunterian Lectures, Jour, of Anat. and Phys.t vol. xxxviii.,
1904.
2 Bonnet, " Beitrage zur Embryologie des Hundes," Anat. Hefte, vol. xx.,
1902.
3 Melissenos, "Ueber die Fettkornchen und ihre Bedeutung in der
Placenta bei den Nagern und der Katze," Arch. f. mikr. Anat., vol. Ixvii.,
1906.
412 THE PHYSIOLOGY OF REPRODUCTION
resulting from the degeneration of the proliferated epithelial
cells. Between it and the spongy layer is the compact layer,
also formed from the sub-epithelial layer. In it the glands are
FIG. 96. — The uterine mucosa of the dog about the twenty-third day of
pregnancy. (From Duval's " Le Placenta des Carnassiers," Journ. de
VAnat. et de la Phys., 1893.)
mes, mesoblast ; tr, trophoblast ; c, capillary layer ; rf, layer of glandular
detritus ; g, glands of compact layer ; Sp, dilated glands of spongy
layer.
FCETAL NUTRITION: THE PLACENTA 413
not so widely dilated and the connective tissue is more
abundant (Fig. 96).
The embryotrophe at this stage differs from that in Un-
gulates. The glandular secretion is less fluid, perhaps because
the lymph transudate is less abundant (Kolster 1). It sur--
rounds the ovum to form the prochorion or " Gallertschicht,"
and is, according to Bonnet,2 absorbed by the trophoblast.
When the prochorion disappears, the foetal ectoderm already
has proliferated over a broad zone of the citron-shaped ovum
(Fig. 97), to form villosities which attack the surface of the
mucosa, and obtain an attachment to it — about the twentieth
FIG. 97- — Ovum with zonary band of villi. (From Hertwig's Entwicklungs-
geschichte des Menschen und der Wirbelthiere, by permission of Gustav
Fischer.)
day in the dog (Duval 3) and the twelfth day in the cat
(Robinson). Vascular processes of the allantois grow into the
centre of the trophoblastic villi, first over a limited discoid area,
and later over the whole zone as the allantois spreads round
the wall. Hence the rudimentary placenta is discoid, and the
completed placenta zonary.
In procuring attachment to the uterus many of the villi
project into glands and crypts. According to Strahl,4 the
epithelium lining the ducts and the surface of the uterine cavity
1 Kolster, " Ueber die Zusammensetzung der Embryotrophe der Wir-
belthiere," Ergebn. d. Anat., vol. xvi., 1906.
2 Bonnet, " Ueber das ' Prochorion ' des Hundekeimblase," Anat. Anzeig.,
vol. xiii., 1897.
3 Duval, " Le Placenta des Carnassiers," Journ. de V Anat. et de la Phys.,
1893.
* Strahl, " Die histologischen Veranderungen d. Uterusepithel. in d.
Kaubthierplacenta," Arch. f. Anat. u. Phys., Supplement, 1890.
414 THE PHYSIOLOGY OF REPRODUCTION
is then transformed into a syncytium and invests the villi
externally. Heinricius l is of opinion that the epithelium dis-
appears, and the syncytium is formed by the uterine connective
tissue. But it is now generally recognised that the syncytium
is trophoblastic. It has been proved by Strahl himself, and by
Duval, that many of the villi obtain attachment at parts of the
surface where there are no gland openings or crypts, and pene-
trate into the substance of the mucosa. Before the disappear-
ance of the epithelium, the cells lose their outlines and form
a homogeneous mass of protoplasm with fragmented nuclei.
This degenerated tissue ought not, as Bonnet 2 emphasised, to
be known as syncytium, which represents an active protoplasmic
condition (see p. 364). The name which he suggested, symplasma,
is very convenient and is used here. It is not only the surface
epithelium which forms a symplasma. The glandular epithelium,
the connective tissue cells, and extra vasated blood may also give
rise to a symplasma which may be designated glandular, con-
nective tissue, and hcematogenous respectively. All are formed to
a large extent in the placenta of Carnivores, and their resem-
blance to the trophoblastic syncytium has led to much confusion.
After the destruction of the epithelium, the villi penetrate,
into the deeper tissues of the mucosa by gradually absorbing
the symplasmata, and branch to form secondary and tertiary
villi. When the ectoderm reaches the capillary layer, it sends
out protoplasmic processes which encircle the dilated vessels.
The trophoblast on the sides of the villi becomes syncytial, but
retains its cellular character at the tips. Internally the villi
contain vascular cores of mesoblast. Hence is formed the
angioplasmode of Duval — a continuous layer of foetal vascular
villi, clad with syncytium, penetrating everywhere into the
capillary layer, and leading to a disappearance of all the maternal
tissues except the vessels (Fig. 98). By the epithelial arcades
at the tips, the layer of villi rests on the sheet of glandular
detritus and the compact layer, which in turn form a symplasma
and undergo absorption. Thus the fcetal structures reach the
1 Heinricius, " Ueber die Entwicklung und Struktur der Placenta beim
Hunde," Arch. f. mikr. Anat., vol. xxxiii., 1889.
2 Bonnet, " Ueber Syncytien, Plasmodien und Symplasma," &c., Monats-
schr. f. Geburtsh. u. Gynak., vol. xviii., 1903.
FCETAL NUTRITION: THE PLACENTA 415
spongy layer, in which the glandular culs-de-sac have expanded
to form large cavities separated by partitions, the mesenteriform
lamellae. Gradually the roof of this layer is also absorbed by
FIG. 98. — The angioplasmode of the dog at the thirtieth day of pregnancy.
(From Duval's "Le Placenta des Carnassiers," Journ de I'Anat. et de la
Phys., 1893.)
ms, mesoblast ; tr, trophoblast ; ae, ectodermic arcades ; d, layer of
glandular detritus.
the trophoblast, and the ectodermal arcades at the tips of the
villi gain a permanent attachment to the mesenteriform lamellae.
At the same time, by the further branching and penetration
416 THE PHYSIOLOGY OF REPRODUCTION
of the foetal mesoderm in the anyioplasmode, the tissue is
broken up into a series of labyrinthine lamellae, which consist of
a network of maternal vessels clothed on each side by syncytial
trophoblast. The meshes of the network are penetrated by
the vessels of the villi. In this way, according to Duval, the
labyrinth is formed. In it the maternal and the foetal blood
are separated by the endothelium of the uterine capillaries, a
cellular layer (considered foetal by Duval and maternal by
Heinricius) which later disappears, the syncytium, mesoblast,
and fcetal capillary walls.
At places, however, the villi come directly in contact with
maternal blood, especially at the " green border " of the placenta,
which forms a characteristic appearance in some of the Carnivora.
In all the members of the order, larger or smaller maternal
haemorrhages occur at an early period after the attachment of
the blastodermic vesicle. The effusions vary in size and position.
In the dog they occur regularly along the margins of the placental
zone, and form the bordure verte ; in addition smaller haemor-
rhages take place into the substance of the placenta, and form
the " green pockets," which may be isolated or joined to the
green border by bridges (Fig. 99). In the cat, the haemorrhages
occur in irregular positions and do not assume the green colour
typical of the dog. Indications of a green border are present in
the earlier stages, but not in the completed placenta. In the
otter and badger, the effusion takes the form of a large blood-
pouch, filled with a great variety of blood derivatives. In the
ferret the conditions are similar ; the main effusion occurs at
the anti-mesometrial border of the uterus, and divides the zone
into two lateral discs. According to Robinson, it lifts the
trophoblast from the decidua, and forces it in the form of irre-
gular pouches towards the interior of the ovum. Strahl and
Bonnet also state that the blood is effused between the mucosa
and the blastodermic vesicle, and thus is contained in spaces
whose walls are maternal on the one side and fcetal on the
other. According to Duval the blood-spaces are entirely lined
by trophoblast, and with the advance of the villi other and
larger haemorrhages occur, coalescing to form the green border
and islands. In either case the trophoblast is in direct contact
with maternal blood. There the wall of the blastodermic
FCETAL NUTRITION: THE PLACENTA 417
vesicle is avillous but strongly folded, the ends of the ectodermal
cells are expanded like clubs, and their protoplasm becomes
coarsely reticular. Into the meshes the constituents of the
green pulpy mass, unaltered erythrocytes and haemoglobin or
its derivatives, are absorbed by phagocytosis.
From the preceding account, it is clear that certain re-
..C ev-c 3 (&m>&?m
»•,««, •-.. ,/f*"l \ ') ,• .. ^•*.-. '"{At >,'-•-' ••'-.-•> ')-'/:'<v U
is >? *v^ X > - 3J? K^.;^^^- -^^ ^^
% ^^M^WK»S
*^-^^^^^ + ^ i -%7^'
"S ^^MBWt
L/^^?
FIG. 99. — The labyrinth and the green border of the placenta of the dog at
the fortieth day of pregnancy. To the right are two lobules of the
angioplasraode which have reached the stage of complexity of the
labyrinthine laraellaj : to the left is the green border, the cavities of
which, normally filled with blood, are indicated by a cross. (From
Duval's " Le Placenta des Carnassiers," Journ. de VAnat. et de la Phys.,
1893.)
1, 2, and 3, basal lamellae of the green border ; 4, basal lamella of lobule
of labyrinth.
semblances and certain differences exist between Carnivora and
Ungulata in the composition of the embryotrophe. The most
notable difference in the zonary placenta is the absence of the
large amount of milky fluid which arises in the sheep from
the glandular secretion and the transudation of lymph. In
Carnivora the gland secretion is less important. Though the
deep parts of the glands which lie in the glandular layer may
2D
418 THE PHYSIOLOGY OF REPRODUCTION
secrete, the epithelium of the more superficial parts proliferates,
and then degenerates and loses its secretory function ; finally
it forms a symplasma which plugs up the lumen of the
glands.
On the other hand, the amount of nutriment furnished
directly from the maternal blood is increased. It is found in
the extravasations already described, and as individual blood
corpuscles and droplets of haemoglobin or its derivatives in the
lumina of glands. Leucocytes are found during the whole of
pregnancy, but in less abundance than in the sheep. They do
not act to the same extent as store-houses of fat, but some of
them, the siderophores, contain granules which give an iron
reaction. In the course of pregnancy they disappear com-
paratively early, with the exception of a few in the deep
glandular layer. Fat is found in the intact epithelium of the
glands, and in the lumen after desquamation of the cells. It
appears in the epithelium partly as an infiltration and partly as
a degeneration product of the protoplasm.
In the Carnivora, the fcetal ectoderm of the zonular band
of attachment attacks the uterine mucosa more strongly than
in the Ungulata. As a result, the maternal tissues, with the
exception of the septa containing the placental vessels, disappear
down to the middle of the spongy layer, and the tissue which is
destroyed serves as pabulum for the developing embryo. Van
der Brock l suggests that the general oedema of the uterine
mucosa may lead, as elsewhere, to its malnutrition and de-
generation, and thus it may fall an easy prey to the trophoblast.
Others maintain that the degeneration is brought about by a
trophoblastic influence, perhaps of the nature of an enzyme
action. The result is a transformation of all the elements to a
symplasma. In the cat the connective tissue cells may form
large decidual cells before their final destruction.
As in the Indeciduates, there is strong histological evidence
that the trophoblast is actively phagocytic, and takes up, as it
meets them, the constituents of the prochorion, and later the
degenerated tissues and extra vasated blood. In the neighbour-
hood of the extravasations active absorption is indicated by the
1 Van der Brock, "Die EihiiUen und die Placenta von Phoca vitulina,"
Petrus Camper, D. ii. Quoted by Kolster (Ergebn. d. Anat., vol. xvi., 1906).
FCETAL NUTRITION: THE PLACENTA 419
change in shape of the trophoblast cells and by their pigmen-
tation. In the mesoblast of the villi and its vessels no trace is
found of any of the formed elements of the embryo trophe, a
proof that they undergo further transformation in the tropho-^
blast after absorption.
The interchange of oxygen and carbonic dioxide apparently
occurs in the labyrinth, as in the cotyledons of the sheep. Here
only is the fcetal circulation brought into close proximity with
circulating maternal blood. Other fcetal waste products are
probably also got rid of in the labyrinth. Nolf 1 suggests that
the excretory products may be responsible for the degeneration
of the maternal tissues into a symplasma.
In how far the other substances necessary for the growth
of the embryo are taken up respectively from the circulating
blood by purely physical or physiologically selective processes,
and from the extra vasated blood effusions by direct phagocytosis,
is not known.
PROBOSCIDEA. — In the elephant, the allantois is large and
vesicular. Short villi are developed over a large area of the
blastodermic vesicle. They lodge in pre-existing depressions
in the uterine wall, but the trophoblast is inactive and does not
attack the maternal tissues (Assheton 2). Over a zonary area,
however, the villi are much longer, and, penetrating deeply
into the maternal tissues, they form a large mass of tissue in
the meshes of 'which maternal blood circulates. Hence the
zonary placenta differs from that of Carnivores and resembles
that of Insectivores, in which, however, the maternal blood
circulates in trophoblastic spaces before the advent of fcetal
capillaries.
Though no red blood corpuscles appear to be absorbed as
such by the trophoblast, there is evidence of an active absorp-
tion of haemoglobin derivatives, the presence of iron compounds
being easily demonstrated, especially in the cores of the villi
1 Nolf, "]£tude des modifications de la muqueuse uterine pendant la
gestation chez le murin," Arch, de Biol., vol. xiv., 1896.
2 Assheton, "The Morphology of the Ungulate Placenta, with Remarks
on the Elephant and Hyrax," Phil. Trans. Roy. Soc., London, Ser. B.,
vol. cxcviii., 1906.
420 THE PHYSIOLOGY OF REPRODUCTION
and the walls of the foetal capillaries. In the syncytial tropho-
blast, however, the Prussian-blue test is negative (see p. 486).
At birth the long villi are left in situ and absorbed by the
maternal tissues.
HYRAX. — As in the elephant, the placenta of Hyrax has been
studied only in isolated specimens, and its development is not
known. According to Assheton,1 the trophoblast is probably
thickened all round the wall of the blastocyst, as in the hedge-
hog and Man, but there is no appearance of a decidua reflexa.
Maternal blood is carried directly to the fcetal side of the tropho-
blast, where it is close to the fcetal vessels, and so may provide
nutriment. It then trickles back through a complicated system
of lacuna in the trophoblast.
The placenta is at first diffuse and later zonary. In the
mucosa of the placental area the glands disappear early, and
a great increase in the inter-glandular stroma occurs, as in
Rodents.2
RODENTIA. — Among the Rodents there are variations in the
mode of attachment. It is centric in the rabbit, excentric in
the mouse and rat, and interstitial in the guinea-pig. In all
the ultimate form of the placenta is discoid.
It was in Rodents that the proliferation and vascularisation
of the trophoblast were first described by Selenka.3 Later
Duval 4 gave a fuller account of the earlier stages, and Hubrecht
discovered the same conditions in other orders.'
Rabbit. — The fertilised ovum of the rabbit, clothed by the
prochorion, reaches the uterus at the beginning of the fourth
day after coitus. At first it has no fixed position ; but by the
1 Assheton, loc. cit.
2 Hubrecht (Quar. Jour, of Micr. Science, 1908) draws attention to the
peculiar position of Hyrax. It has many archaic peculiarities, and has
been placed near Rodents, elephants, and Ungulates by different authors.
Yet its placental characters resemble those of the hedgehog and Man. This
he takes as strong evidence that the type of placenta found in Hyrax, the
hedgehog, and Man, diverges less widely from the primitive type than the
placenta of Ungulates and Rodents.
3 Selenka, Keimbldtter und Primitivorgane der Maus, 1883.
4 Duval, " Le Placenta des Rongeurs," Journ. de VAnat. et de la Phys.,
1889-92.
FCETAL NUTRITION: THE PLACENTA
seventh day, when the blastocyst is about five millimetres in
diameter, the prochorion lies so closely on the surface of the
uterus that it fixes the ovum. At the end of the eighth day
the prochorion ruptures, and the blastodermic vesicle probably_
collapses at the same time by injury to its wall.1
The " mature " uterine mucous membrane of the non-
pregnant rabbit already shows specialised structures, which are of
importance for the attachment and nutrition of a future embryo.
These consist of symmetrical pairs of longitudinal folds, first
described by Hollard,2 and subsequently named by Minot : 3
FIG. 100. — Transverse section of a four days' gestation sac of the rabbit.
The mucosa is differentiated into six definite folds. The two folds
nearest the mesometrium are the largest and mark the site of placental
attachment. (From Chipman's "The Placenta of the Eabbit," Labor.
Rep., Roy. Coll. Physic., Edinburgh, vol. viii., 1903.)
p, p', placental folds ; n, n', peri-placental folds ; o, o', ob-placental folds.
placental folds, the largest, situated one on each side of the
groove corresponding to the insertion of the mesometrium ;
ob-placental folds, the smallest, opposite the mesometrium ;
peri-placental folds, intermediate in position and size (Fig. 100).
Each fold is divided by transverse fissures into rectangular
areas, the coussinets of Hollard. At the onset of pregnancy two
of these areas on the placental folds, placed one on either side
of the mesometrial groove, hypertrophy and form the maternal
part of the future discoid placenta (BischofI 4), which is thus
1 See Hertwig's Entwicklungsgeschichte des Menschen und der Wirbelthiere,
1906.
2 Hollard, "Recherche sur le Placenta des Rongeurs," Annales des
Sciences Naturelles, 1863.
3 Minot, " Die Placenta des Kaninchens," Biol. CentralbL, vol. x., 1890.
4 Bischoff, Entwickelung des Kaninchen-Eies, Braunschweig, 1842.
THE PHYSIOLOGY OF REPRODUCTION
bi-lobed (Fig. 101). The folds of the mucosa are essentially
increased areas of the mucosal connective tissue, but they differ
from the cotyledons of Ruminants in having glands.
On the entrance of a fertilised ovum into the uterus, the
folds, especially the ob-placental, become shortened, and a
localised actual cavity appears which is occupied by the blasto-
cyst. At the same time there is a marked hyperplasia of the
cellular connective tissue of the placental and peri-placental
folds, leading to a thickening of their bases (Chipman *). By the
FIG. 101. — Transverse section of a seven days' gestation sac of the rabbit
(Chipman). The placental folds (coussinets) are large (a) ; the muscular
walls of the sac are thin.
sixth day, the capillaries are also increased in these regions.
In the ob-placental folds appear enormous giant-cells, derived
by a process of " degenerative hypertrophy " from the
epithelium of the surface and glands. They persist till the
fourteenth day, and are probably absorbed by the trophoblast
overlying the yolk-sac. In the placental lobes the epithelial
1 Chipman, " Observations on the Placenta of the Rabbit, with Special
Reference to the Presence of Glycogen, Fat and Iron," Laboratory Reports,
Roy. Coll. Phys., Edinburgh, vol. viii., 1903. The development of the
placenta is carefully traced in a complete age-series of pregnant rabbits
and admirably figured by many photo-micrographs. The account as given
here is based mainly on Chipman's monograph, but the phraseology is some-
times changed.
FCETAL NUTRITION: THE PLACENTA 423
cells proliferate and fill up the superficial culs-de-sac of the
mucous membrane. The glands are as yet unchanged, and
the increased blood supply leads to a free secretion which is
usually considered to be added to the albumen-layer, and then_
to fete absorbed by the trophoblast. There is no appreciable
transudation of lymph such as occurs in Ruminants.
As the blastodermic vesicle grows, it presses against the
folds and levels them. Hence at the time of attachment the
surfaces of the placental lobes are nearly regular. The covering
epithelium again returns to normal, but the active proliferation
of the connective tissue cells is continued to form the placental
cotyledons. At the same time the trophoblast proliferates in
concentric areas on either side of the embryonic rudiment,
which is placed opposite the groove between the placental
cushions. Here the ovum is generally said to gain its first
attachment, the ob-placental lobes having by this time dis-
appeared.1
Where the maternal and foetal tissues are in contact, the
surface epithelium shows a form of degeneration similar to the
epithelial symplasma of the zonary placenta — fusion of cells and
fragmentation of nuclei. It is attacked by the thickened,
horseshoe-shaped trophoblast, the ectoplacenta of Duval, and
its edge presents microscopically a " bitten or corroded ap-
pearance/' This phagocytic or chemical action leads later to
the complete disappearance of the epithelium, so that the
trophoblast comes in contact with the connective tissue of the
uterus. The glands are dilated, and their proliferated endo-
thelium forms a symplasma which blocks the lumina. At
these places the trophoblast advances more quickly, as if the
resistance was weaker, and the line of attachment . is undulating
(Fig. 102). The dips thus correspond to the gland orifices and
represent the beginnings of the future villi. The blood-vessels
are large and numerous and have no adventitia, i.e. they are
wholly capillaries. But the more deeply placed of them
acquire an adventitia, the perivascular sheath (Masquelin and
1 Assheton (Quar. Jour. Micr. Sci., vol. xxxvii., 1895) states that the
trophoblast shows papillary thickenings over the ob-placental and peri-
placental lobes, and that by them the ovum obtains the first attachment
over its lower pole.
424 THE PHYSIOLOGY OF REPRODUCTION
Swaen l). It is formed of one or two layers of large connective
tissue cells which represent the first appearance of the decidual
cells. After the destruction of the superficial and glandular
epithelium, the trophoblast advances into the interglandular
tissue, the cells of which degenerate in turn and are absorbed.
The advance is most rapid where a capillary is met with.
FIG. 102. — Thickened ectoderm (ectoplacenta) in the rabbit, attached to
placental lobe and dipping more deeply at the position of the glands.
(Chipman.)
ec, foetal ectoderm ; I, line of attachment of ectoderm ; d, fcetal ectoderm
dipping into placental gland ; g, terminal cul-de-sac of placental gland.
The mucous membrane is now differentiated into two zones,
the intermediary region and the region of the uterine sinuses
(Duval). The intermediary region lies superficially. It is
closely packed with fusiform stroma cells and capillaries with
thin peri vascular sheaths of uninucleate decidual cells. "It
suggests a reaction of the maternal placenta to the ' parasitic '
1 Masquelin and Swaen, " Developpement du placenta maternel chez le
lapin," Bull, de VAcad. Roy. de Belg., 1879.
POSTAL NUTRITION: THE PLACENTA 425
foetal placenta " (Chipman ; see also p. 369). By the influence
of the trophoblast the decidual cells increase in size and
become multinudeate (Maximow 1). They lose their peri-
vascular position and pervade the whole of the region. In their_
formation all traces of the gland ducts are lost, the cells of the
latter appearing to serve as pabulum for the decidual cells.
In the region of the uterine sinuses the blood-vessels dilate
to form large spaces, and the decidual cells remain uninucleate
till a considerably later period. The junction between the two
zones is marked by the blind ends of the glands, which are
rilled with degenerated epithelium. In section each appears as
an island of glandular symplasma.
At the tenth day the allantois joins the outer wall of the
blastocyst over the site of the future placenta. The trophoblast
of this region is differentiated into two layers, the plasmodiblast
and the underlying cytoblast. The latter disappears before the
end of pregnancy. Processes of vascular mesoblast invade the
trophoblast at intervals, and break it up into columns. At the
same time the foetal tissues continue to advance and surround
maternal capillaries, the endothelium of which they replace.
In the zonary placenta of Garni vora the trophoblast surrounds
the vessels without destroying the endothelium. In the rabbit
the ectodermal processes are hollow tubes which surround" the
vessels ; they are closed on the fcetal side and open on the
maternal side. Their cavity is filled with maternal blood, and
externally lies the cytoblast and vascular mesoblast. Such are
the " villi." Subsequently the arrangement becomes more
complex, each hollow column being divided up into a series of
hollow tubes parallel to the original column, and each tube in
turn forming a series of hollow tubules. At each division the
thickness of fcetal tissue between the maternal blood in the
axis and the foetal vessels decreases, till finally there is only a
film of trophoblast and the vascular wall. At places the
trophoblast even is wanting, and the fcetal endothelium alone
intervenes between the two blood-streams.
The endothelium of the maternal capillaries frequently
ruptures just before it is overtaken by the ectoderm, and irre-
1 Maximow, " Zur Kenntnis des feineren Baues der Kaninchen-Placenta,"
Arch.f. mikr. Anat., vol. li., 1897. See also ibid., vol. Ivi., 1900.
426 THE PHYSIOLOGY OF REPRODUCTION
gular blood extravasations are formed, and later surrounded by
trophoblast. In the deeper layers of the intermediary region,
according to Chipman, capillary haemorrhages occur more
slowly, and give rise to a fibrinous tissue with red and white
blood corpuscles scattered through it. This is similar to the
hsematogenous symplasma of Bonnet. It gradually increases in
amount, and extends to the region of the uterine sinuses.
While the foetal ectoderm advances along the vessels, it
remains stationary at the non- vascular parts. Hence there is
an interlocking of maternal and foetal tissues, and peninsulae of
multinucleate cells come to lie between the projections of the
trophoblast. At the same time the intermediary region de-
creases in thickness, and the ectoderm reaches the superficial
sinuses of the deeper zone. Here the uninucleate decidual cells
again become multinucleate, apparently at the expense of the
blood symplasma, in the same manner as formerly at the ex-
pense of the glandular symplasma. The sinuses enlarge, and
their walls proliferate into several layers of degenerated cells,
which after mid- term are gradually replaced by laminie of
fibrin.
At a later period the intermediary zone still further de-
creases in thickness, and the multinucleate cells gradually
" melt to form a granular detritus " (Duval). At the end of
pregnancy the maternal placenta consists almost entirely of
blood and blood symplasma, except for a thin rim of tissue
containing blood-sinuses at the zone of separation. The gesta-
tion period is thirty days.
As compared with the placenta of Carnivora, it is obvious
that the dilatation of maternal vessels is much more marked in
the rabbit, and throughout the placenta the maternal blood is
in direct contact with the trophoblast, and not only at the
border or round a blood-pouch. The blood is not degenerated
to a sufficient extent to exhibit the varieties of pigmentation
found in the zonary placenta. Chipman does not state whether
the maternal blood circulates in the trophoblastic tubes, but
Maximow l says that it does. Similarly Duval says : ''' The
maternal blood circulates from the foetal extremity towards the
1 Maximow, " Die ersten Entwicklungsstadien der Kaninchenplacenta,"
Arch.f. mikr. Anat., vol. Ivi., 1900,
FCETAL NUTRITION: THE PLACENTA 427
maternal extremity of a lobule " (i.e. the series of tubules de-
rived from one tube). According to Masius,1 " the maternal
blood circulates in an ectodermal mass of foetal origin/' Herein
lies a great difference between the placentae of Rodents and^
Carnivores or Ungulates. In the sheep the main nutriment is
furnished by the glands ; the maternal blood which is in contact
with foetal ectoderm is stationary and small in amount, and
serves chiefly as a supply of iron ; the exchange of gases takes
place through foetal and maternal tissues. In the dog the
gland secretion is less important ; the blood is again stationary
and restricted to certain situations, and it shows markedly
degenerative appearances, but it is greater in amount, and
probably furnishes other substances besides iron for the foetus ;
in the angioplasmode the maternal blood circulates and here the
exchange of gases is effected, but again both maternal and
foetal tissues intervene between the two blood-systems. In the
rabbit the glandular secretion is still less important after attach-
ment, and even the blind ends do not secrete ; throughout the
placenta there is normal circulating maternal blood in direct
contact with foetal tissues, and it serves both as nutriment and
for the exchange of gases. In addition, there are stationary
blood extravasations which are engulfed by the trophoblast, but
they are subsidiary. Both in the dog and the rabbit there is a
marked formation of symplasma which may be connected, as
Bonnet suggested for the dog and Maximow for the rabbit, with
the slowing of the circulation in the placenta, or may be the
result of a trophoblastic influence.
In the placenta of the rabbit there is one other difference
which marks it off from the placenta of Carnivores and links it
with Insectivores and Man — the connective tissue cells of the
mucosa form decidual cells. They assist to an important degree
in the preparation of nutriment for the embryo. They exercise
a phagocytic action on the neighbouring degenerated maternal
tissues, glandular remnants and fibrin, and so attain their
greatest development, while at the same time they become
store-houses of foetal nutriment. At a later period they de-
generate and are absorbed by the trophoblast. Their possible
1 Masius, "De la Genese du Placenta chez le Lapin," Arch. de. Biol.,
1889.
428 THE PHYSIOLOGY OF REPRODUCTION
function as a protection against the attack of the foetal ectoderm has
already been mentioned. At the end of pregnancy their defence
is no longer required, as the trophoblast has also lost its activity.
Iron Metabolism. — The decidual cells are concerned in the
metabolism of iron, fat, and glycogen for the foetus. In the
rabbit, as contrasted with Ruminants, the ingestion of healthy
or degenerated erythrocytes probably does not occur. Though
Maximow states that they are " present in the plasmodium,"
they appear to be in the plasmodium only as the isolated penin-
sulae of decidual cells are in it, i.e. they lie in spaces surrounded
by trophoblast. Whether haemoglobin as such, or its more
immediate derivatives in the form of organic iron compounds
are absorbed has not been investigated, but Chipman has shown
that inorganic iron compounds are present, and their distribution
speaks for their absorption by the trophoblast. The compounds
appear as blue-black granules in sections stained with a weak
watery solution of haematoxylin. At the fourteenth day they
are present in the fcetal mesoblast, especially where it approaches
the decidua. They increase in size and number for a few days
and then diminish, but some are still seen at the end of preg-
nancy. A few granules appear in the trophoblast between the
sixteenth and twentieth days (Fig. 103). From the sixteenth
day they are also found in an increasing number of the decidual
cells which lie close to the fcetal placenta ; after the twenty-
fourth day, when the cells degenerate, the granules are no
longer discrete, but there are irregular blue-black patches up to
the end of pregnancy.
Such isolated data cannot be accurately interpreted. The
fact that the deposits in the three tissues are always situated in
apposition to each other speaks for their absorption by the
foetal tissues ; on the other hand, a very small number of
granules are present in the trophoblast, and only for a few days.
It is possible that organic iron compounds, not shown by the
haematoxylin stain, are absorbed and broken up, and later
appear as granules in the mesoderm. Their further course to
the fcetal liver, in which they are stored, has not been traced.
It is to be noted that the iron compounds are not only derived
from haemoglobin. They may also represent degeneration pro-
ducts of the nucleoproteins.
FCETAL NUTRITION: THE PLACENTA 429
Hubrecht 1 has suggested that erythrocytes may be manu-
factured in the decidual cells, and their iron-containing granules
may thus be utilised (see p. 494).
Fat Metabolism. — Regarding the presence of fat in the
YIG. 103. — Iron granules in the placenta of the rabbit at the eighteenth day
of pregnancy. (Chipman.)
a, iron granules in mesoblast ; 6, iron granules in multinucleate decidual
cells ; g, iron granules in ectodermal tubules.
1 Hubrecht, "Ueber die Entwicklung der Placenta von Tarsius und
Tupaja," Internat. Congr. ofZool., Cambridge, 1898.
430 THE PHYSIOLOGY OF REPRODUCTION
placenta of the rabbit, a few observations have been made by
Eden,1 Maximow, and Masius. Chipman has investigated the
subject in greater detail, but he draws no conclusions from the
histological data. In reality, the study of fat in the placenta
is rendered difficult by its occurrence both as an infiltration
and in the degeneration of cells.
Fat is found in the fcetal viscera, liver, heart, and mid-gut,
before the allantoic circulation is established. At this time,
the tenth day, the vitelline circulation is at its height, and the
fat probably reaches the embryo by its vessels, as it is also
found in the hypoblast of the area vasculosa. It may be de-
rived from the absorption by the trophoblast of fat-droplets
contained in the giant-cells of the peri-placental folds. As the
vitelline circulation diminishes, the fat disappears from the
embryonic viscera, and does not reappear till four or five days
after the establishment of the allantoic circulation. During this
interval fat is present in the extra-placental wall of the blasto-
cyst, but it probably arises by a degeneration of its cellular
protoplasm.
In the fcetal placenta, fat is never found in the mesoblast or
capillary walls, but it occurs in the trophoblast, especially
where it is in contact with maternal blood or decidua. It in-
creases from the twelfth to the sixteenth day, then it decreases,
and a week later disappears altogether. In the maternal
placenta fat first appears in the decidual cells which are
nearest the trophoblast. They show no sign of degeneration
at this time, and they probably secrete the fat globules. After
increasing for a few days, it diminishes with the atrophy of the
decidual cells, and finally appears as fatty debris. Fat is also
present in the proliferating endothelium, and later in the fibrin
lamina) of the uterine sinuses.
In the new-born foetus the main store of fat is contained
in the subcutaneous tissue. It is remarkable that it does not
appear in this situation till the greater part of the fat has dis-
appeared from the placenta. It is either transmitted to the
foetus in a form which does not reduce osmic acid, or formed in
the foetus itself .from other substances. At birth the fcetal
1 Eden, "The Occurrence of Nutritive Fat in the Human Placenta,"
Proc. Roy. Soc., London, vol. lx., 1896.
FCETAL NUTRITION: THE PLACENTA 431
viscera, especially the liver, have a considerable store of fat
which increases during suckling.
Glycogen Metabolism. — The presence of glycogen in the
placenta of the rabbit was discovered by Claude Bernard * in
1859. He showed its increase and subsequent decrease during -
pregnancy, and concluded from his observations that the
placenta carried out for the foetus, in the first half of intra-
uterine life, the glycogenic function subsequently assumed .by
the foetal liver. Godet 2 described two areas of glycogen-con-
taining cells, one immediately underlying the foetal villi, the
other in the deeper part of the placenta. Maximo w investigated
these cells at different stages of pregnancy ; he found glycogen
in the decidual cells of the vascular sheaths at the eighth day,
gradually increasing in amount and playing an important part
in the nourishment of the trophoblast. In the later stages
glycogen disappeared and the decidual tissue was transformed
into polygonal multinucleate cells rich in fat. Chipman recorded
detailed observations in a more complete age-series from the
eighth day to the end of gestation. He showed that glycogen
was always present in the maternal part of the placenta, but
never in the foetal. Occurring in the decidual cells of both zones,
it increased and reached a maximum between the twelfth and
sixteenth days (Fig. 104) ; then it steadily diminished, and in
the last week only a few granules were found scattered in the
conglomerate masses of decidual cells. At the zone of separa-
tion, however, glycogen granules were still contained in decidual
cells. Chipman also examined the fcetal liver. In it he found
that glycogen appeared at the twenty-second day, and increased
rapidly and steadily in amount till the end of pregnancy.
These results have for the most part been corroborated by
chemical analyses carried out by the writer, working in colla-
boration with Dr. W. Cramer.3 They determined quantitatively
the glycogen of the maternal placenta, fcetal liver, and remainder
1 Bernard, "Sur une nouvelle fonction du placenta," Comp. Rend. Acad.
Sci., Paris, 1859.
2 Godet, "Recherches sur la structure intime du placenta du lapin,"
Dissert. Inaug. d la Fac. de Med. de Berne, Neuveville, 1877.
3 Lochhead and Cramer, " The Glycogenic Changes in the Placenta and
the Foetus of the Pregnant Rabbit," Proc. Roy. Soc., London, B, vol. Ixxx.,
1908.
432 THE PHYSIOLOGY OF REPRODUCTION
of the foetal body in an age-series of pregnant rabbits from the
fourteenth day to the end of pregnancy. The maternal placenta
Jp
e t>
» *»,«;•
» «
&
§
•}
a ,."
" ^ f * 4 *e!\ ^v^
^5
-^5"
FIG. 104. — Glycogenic areas of the rabbit's p'acenta at the twelfth day of
pregnancy. (Chipman.)
fp, ftetal placenta, containing no glycogen ; ir, intermediary region ; re,
region of uterine sinuses ; ss, uterine sinuses with perhascular sheaths
of uninucleate cells rich in glycogen ; </, glycogen granules in multi-
nucleate cells; m, muscular wall immediately above which, at a later
date, the zone of separation, containing glycogenic decidual cells, is
differentiated.
was separated mechanically from the foetal placenta, and each
was investigated separately. The maternal part includes the
two glycogenic areas, the region of the uterine sinuses and the
FCETAL NUTRITION: THE PLACENTA 433
zone of separation. The foetal part includes the peninsula of
decidual tissue which form the intermediary zone ; the glycogen
contained in it belongs wholly to these peninsulas and represents
the fraction most intimately related to the trophoblast. It may
on that account be termed the proximal glycogen, while that
of the maternal part is the distal glycogen. On the fourteenth
day the distal glycogen forms over 4 per cent, of the weight of
the maternal part, and it gradually increases till the eighteenth
day, when it forms 5 '5 per cent. ; it remains nearly constant till
the twenty-second day, and then there is a continuous decrease
each day till the end of pregnancy. On the day before labour
it amounts to slightly over 1 per cent., and practically the whole
of it is situated at the zone of separation. This last is probably
not destined for the foetus.
The variations in the proximal glycogen are similar. At the
twenty-ninth day there is no glycogen left in the intermediary
region.
In the foetal liver traces of glycogen are present at the
eighteenth day, though none can be demonstrated histologi-
cally till four days later. Up to the twenty-fourth day the
percentage gradually increases, but is still very small. Next
day it rises for the first time above the glycogen percentage in
the rest of the foetal body, and then there is a rapid increase till,
on the twenty-ninth day, half of the foetal glycogen is stored in
the liver. Hence it may be concluded that, although the liver
contains glycogen in the earlier stages, a change occurs at the
twenty-fifth day of pregnancy. Only then does it store more
than its proportion of glycogen by weight, and thus may be
said to be capable of carrying on the glycogenic function for
the foetus. Before that date the only store of glycogen avail-
able is contained in the maternal placenta. '' The glycogen
metabolism of the placenta and foetus shows a regular suc-
cession of changes which proceed almost regardless of external
conditions, and which are independent to a great extent of the
glycogen metabolism of the mother " (Lochhead and Cramer).
There can be little doubt that the glycogen stored in the
decidual cells is absorbed by the trophoblast. It is situated in
the maternal peninsular which are surrounded by foetal tissue,
and it gradually decreases in amount while it increases in the
2E
434 THE PHYSIOLOGY OF REPRODUCTION
foetus. That none can be demonstrated in the trophoblast may
be due to a transformation into sugar before it is absorbed.
Glycerine extracts of both the maternal and the fcetal part of
the placenta possess an enzyme which has a powerful hydrolytic
action on glycogen. On the other hand, the enzyme action is
markedly weaker, or absent altogether, in the placentae of
Ruminants, in which the glycogenic changes are known to be
insignificant.
It is not easy to determine why such a complex mechanism
is necessary if, as is stated by Cohnstein and Zuntz,1 glucose
passes from the maternal to the foetal circulation by diffusion.
But these investigators have only proved that it diffuses when
a hyperglycaemia exists in the mother. Under similar con-
ditions glucose passes into the urine and liquor amnii in Man,
but it does not pass normally.2 Hence it has not been proved
that the sugar of the maternal blood is diffused unchanged
through the trophoblast. It is more probable that the trans-
ference of sugar is not effected by a purely physical process,
since the serum of the fcetal rabbit contains laevulose, while
the serum of the mother has none (Pa ton, Kerr, and Watson 3).
Between the glycogen metabolism and the growth of the
foetus there is a distinct relationship, which probably depends
directly on the uses to which glycogen is put. Part of it is
accounted for by the intense carbohydrate metabolism which
proceeds in the foetus (Bohr4). The glycogen, which is thus
katabolised, furnishes thereby the energy necessary for the
formation of new tissues, the " Entwicklungsarbeit " of Tangl.5
The question arises whether glycogen also performs anabolic
1 Cohnstein and Zuntz, " Weitere Untersuchungen zur Physiologic der
Saugetierfotus," Pflilger's Arch., vol. xlii., 1888.
2 Even in the hyperglycaemia of diabetes the figures do not support the
theory of the mere diffusion of glucose. Offergeld found 0'8 per cent, of sugar
in the maternal blood, and 2*2 per cent, in the foetal blood in diabetic coma
(" Ueber das Vorkommen von Kohlehydraten im Fruchtwasser bei Diabetes,"
Ze.it. f. Geb. u. Gynak., vol. li.).
3 Paton, Kerr, and Watson (B. P.), "On the Source of the Amniotic and
Allantoic Fluids in Mammals," Trans. Roy. Soc. Edinburgh, vol. xlvi., 1907.
4 Bohr, "Die respiratorische Stoffwechsel des Saugetierembryos," Skand.
Arch. f. Phys., vol. x., 1900. See also vol. xv., 1904.
6 Tangl, " Beitrage zur Energetik der Ontogenese," Pjluger's Arch.,
vol. xciii., 1903.
FCETAL NUTRITION: THE PLACENTA 435
functions in the development of the foetus. ' The absence of
glycogen from some of the growing foetal tissues, and the fact
that many of the tissues in which it is present do not contain
even as much as the adult ones, leave little doubt that a definite
formative power cannot be attributed to glycogen as such. Onr
the other hand, the scarcity of glycogen in embryonic tissues
does not necessarily justify the conclusion that glycogen does not
take part in the building up of the tissues. It is well known
that embryonic tissues are rich in mucin, which contains a large
amount of a carbohydrate group in its molecule. Although
glycogen as such has no formative power, it may yield one of
the " Bausteine " for the building up of the main protein body
of fcetal tissues. In this connection it is interesting to consider
the conditions in the hen's egg, which contains in itself the
material of which the embryo is built up.1 In the ovum carbo-
hydrate as such is practically absent. At the same time all the
protein substances of the white of egg are distinguished by the
presence of a large amount of glucosamine in their molecule. Here
the carbohydrate group has entered into the protein molecule, and
correspondingly there is a scarcity of free carbohydrate/' 2
Protein Metabolism. — In so far as the influence of the tropho-
blast on proteins has been investigated in the placenta of the
rabbit, it may be considered here. It is generally accepted that
colloid substances with large molecules, which are not adapted
for diffusion, require a preliminary transformation, by which the
size of the molecules is decreased before they can be taken up
by the fcetal ectoderm. But the actual observations are against
such a general statement. In the sheep the trophoblast can
absorb not only haemoglobin, a colloid, without any preliminary
transformation, but even enormously larger masses of proto-
plasm in the form of cells. On the other hand, such hydrolysed
products of albumen as albumoses and peptone are not present
in the fresh placenta, nor can any extra-cellular proteolytic
enzyme be extracted.3 Hence there is no evidence of a placental
1 Compare Emrys-Roberts, "A Further Note on the Nutrition of the Early
Embryo, with Special Reference to the Chick," Proc. Roy. Soc., London, B.,
vol. Ixxx., 1908.
2 Lochhead and Cramer, loc. cit.
3 Lochhead, "On the Transmission of Nitrogenous Compounds from
Mother to Foetus," Trans. Obstet. Soc., Edinburgh, vol. xxxiii., 1907-8.
436 THE PHYSIOLOGY OF REPRODUCTION
digestion of proteins before their absorption by the trophoblast.
Further it has been shown, by means of the precipitin reaction,
that if egg-albumen is injected into the mother some of it passes
unchanged to the foetus (Ascoli l). On the other hand, the
proteins of ox-serum cannot be recognised in the foetal blood,
even when a considerable quantity is injected.2 The reason
appears to be that the proteins of ox-serum resemble more
closely the normal serum proteins of the rabbit and are meta-
bolised by the trophoblast, while egg-albumen cannot be utilised,
and is passed on to the foetal circulation unchanged. Hence it
is probable that the normal proteins of the serum are also
transformed by the trophoblast into a form suitable for the
foetus. The exact nature of the transformation is unknown,
but it is not comparable with the hydrolytic processes which
occur in the intestine.
Respiration. — According to Bohr,3 the foetal rabbit absorbs
slightly more oxygen and gives off slightly more carbonic acid
per kilogram per hour than the mother. Hence the intensity
of the metabolic reactions is slightly greater in foetal life. This
is directly opposed to the views held by Pfliiger on theoretical
grounds, and by Cohnstein and Zuntz 4 from their experimental
results. The second result of Bohr's experiments has been
already mentioned, viz. that in that part of the metabolism
which is evidenced by the respiratory exchange, the energy
arises from carbohydrates. He supposes that the energy
liberated by the combustions, which in the adult is dissipated
largely under the form of heat radiated and water evaporated
from the surface of the body, is in the foetus used for the in-
crease and maintenance of the newly formed tissues ; in other
words, " the reactions of synthesis, which are so numerous
during development, are endothermic or heat-absorbing, and
they borrow the heat from other simultaneous exothermic
actions," 5 in this case the oxidation of carbohydrates.
1 Ascoli, "Passiert Eiweiss die placentare Scheidewand ? " Zeit. f. phys.
Chem., vol. xxxvi., 1902. This has been confirmed by the writer and Dr. W.
Cramer (see reference, note 3, p. 435).
2 Lochhead, loc. tit. s Bohr, loc. cit.
4 Cohnstein and Zuntz, " Untersuchungen iiber das Blut, den Kreislauf und
die Atmung der Saugetierfotus," Pfluger's Arch., vol. xxxiv., 1884.
s See Richet's Dictionnaire de Physiologic, vol. vi., Article "Foetus."
FCETAL NUTRITION: THE PLACENTA 437
Mouse. — The fertilised ova of the mouse reach the uterine
cavity on the third day, and segmentation is completed one day
later. The zona pellucida has by this time disappeared, and
fixation of the ovum to the uterus can be quickly attained^
Each blastocyst comes to rest in an an ti-mesome trial groove.
At first spherical, it becomes ovoid on the sixth day, with the
long axis perpendicular to the long axis of the uterus. One pole
is turned towards the mesometrium and is composed of several
layers of cells, while the opposite pole is single-layered. It is
nourished by the glandular secretion, and perhaps also by a
transudate, in which, however, leucocytes are not present.
The connective tissue of the mucosa shows a thickening at
the point where a blastocyst rests. The epithelium degenerates
as the result of contact with the foetal ectoderm (Duval 1), or
of pressure by the proliferated connective tissue cells which
interferes with the nutrition of the epithelium (Burckhard 2).
More probably it is not mechanical, as the change begins first
at the mouth of the groove, i.e. at the point of first contact
with the ovum (Kolster 3). In the cells the chroma tin clumps
on the inner surface of the nuclear membrane, the cell boundaries
disappear, and a symplasma is formed which later becomes
broken up into nuclear and cellular fragments. Fat globules,
which are present in the epithelium of the non-pregnant uterus,
are found in the detritus and also in the foetal ectoderm.
With the destruction of the epithelium appears the first sign
of decidual formation. The connective tissue cells increase in
size and displace the glands ; the capillaries dilate irregularly,
and at places form sinuses.
On the sixth day, the ectoplacental cone is formed by a pro-
liferation of the ectoderm at the mesometrial pole of the blasto-
cyst. It plugs the opening between the crypt and the lumen
of the uterus. At the same time the lips of the crypt are
gradually brought nearer to each other by the swelling of the
tissues, and at the end of the seventh day they fuse and cover
1 Duval, " Le Placenta des Rongeurs," Journ. de VAnat. et de la Phys.,
1891.
2 Burckhard, " Die Implantation des Eies der Maus in die Uterinschleim-
haut," Arch. f. mikr. Anat., vol. Ivii., 1901.
3 Kolster, " Zur Kenntnis der Embryotrophe beim Vorhandensein einer
Decidua Capsularis," Anat. Hefte, vol. xxii.
438 THE PHYSIOLOGY OF REPRODUCTION
the ectoplacenta. In this way the ovum is completely shut off
in a decidual cavity, the " Eikammer," from the uterine lumen.
The roof of the chamber forms the primary decidua reflexa,
and it is gradually thickened by a decidual deposit. In it new
blood-vessels are developed, and they form a specially rich
vascular network.
By this time the blastocyst has become tubular in shape,
and it shows an inversion of
the germinal layers (Fig. 105).
In the earlier stage a cavity
appears in the inner mass of
cells. The roof of the cavity
becomes thickened to form the
" Trager " or ecto - placental
cone, which is at first cylindrical
and later conical, with its base
resting on the mesometrial pole
of the ovum. By its inward
FIG. 105. — Inversion of the germinal . * .
layers in the blastodermic vesicle growth, it shoves before it the
of the mouse. The trophoblast floor of the inner mass consist-
becomes greatly thickened and • of epiblast and hypoblast.
invaginated, pushing the for- T , , . . . , .
mative epiblast before it. The In thls ™7 an Imagination IS
whole blastocyst assumes a tubular produced in the tube with the
epiblast internal to the hypo-
blast. Hence the germinal
layers are said to be inverted.
Blood is regularly found
jn ^ implantation cavity. It
, , '
completely surrounds the ovum,
and reaches irregular spaces in
the ectoplacenta which communicate with the surface. At
this time, however, there are no fcetal vessels near the cone,
and the blood in its meshes may be of use only for its own
nutrition. On the other hand, the thin -trophoblast of the
wall of the invaginated yolk-sac is partly vascularised by
vitelline vessels, by means of which the nutriment absorbed
from the blood effusion may reach the embryo, or be
stored in the yolk-sac. In the trophoblast itself the
haemoglobin of laked corpuscles and its derivatives are
shape, and the hypoblast appears
to be external to the epiblast.
Trophoblast represented by con-
tinuous black lines or masses :
entoderm by interrupted lines :
embryonic ectoderm by epithelial
cells. (T. H. Bryce, in Quairis
Anatomy, Longmans.)
FCETAL NUTRITION: THE PLACENTA 439
present (Jenkinson 1), and the contents of the umbilical vesicle
are " not yolk, but another nutritive substance which the
ovum, in the absence of yolk, takes from the maternal tissues,
viz. haemoglobin " (Sobotta 2).
The decidual cavity is at first small and ovoid, and has a~
thick wall. As it grows, the lumen of the uterus is obliterated,
and at its point of contact with the mesometrial wall the epi-
thelium of the latter disappears. Thereafter the two layers
fuse, and at the point of fusion the placenta is developed. The
lumen of the uterus is later re-established, as in the guinea-pig
(see Fig. 110), at the floor of the decidual cavity. Hence the
primary decidua reflexa forms the serotina, and a secondary
reflexa is formed, which is recognisable till the twentieth day
of pregnancy.
The increase in size of the implantation cavity is accom-
panied by a thinning of its wall. According to Duval this is a
mechanical process, since the cells do not increase in number,
but it is probably more complicated. On the inner surface of
the decidua giant-cells appear around the ovum, and they are
phagocytic (Fig. 106). Duval stated that each was derived from
a cell of the foetal ectodermal wall of the yolk-sac, and later
from a cell of the ectoplacental cone. As they increase in
number, they form a distinct layer, two to five cells in depth,
between the yolk-sac and the wall of the implantation cavity,
and some wander into the decidua and lie singly or in groups.
In their interior degenerating leucocytes are frequently seen.
Sobotta also stated that they were foetal in origin, and helped to
fix the ovum and erode maternal capillaries. More recently
Kolster has brought forward evidence from their histological
appearance that they are -transformed decidual cells, and this is
strongly supported by Disse's investigations on the field-mouse,3
in which the giant-cells are found before the ovum has become
embedded, and the first to appear are at an appreciable dis-
tance beneath the surface epithelium. A second series of
1 Jenkinson, "Observations on the Histology and Physiology of the
Placenta of the Mouse," Tijd. Nederl. Dierk., Ver. ii., Dl. vii.
2 Sobotta, "Die Entwicklung der Maus," Arch. /. mikr. Anat., vol. Ixi.,
1903.
3 Disse, "Die Vergrosserung der Eikammer bei der Feldmaus," Arch. f.
mikr. Anat., vol. Ixviii., 1906.
440 THE PHYSIOLOGY OF REPRODUCTION
smaller size appears later in the lumen and wall of the implanta-
tion cavity. Jenkinson also recognised two groups, but assigned
mpfi.
FIG. 106. — Longitudinal section of the implantation cavity of the field-
mouse about the eighth day of pregnancy. (From Disse's "Die
Vergrosserung der Eikammer bei der Feldmaus (Arvicola arvalis)," Arch,
f. mikr. Anat , vol. Ixviii., 1906.)
p.l., placental pole ; mph, macrophages or giant-cells ; sym, uterine
symplasma ; I, blood lacuna.
to them different origins, foetal in the " Eikammer " and
maternal in the decidua.
All authorities agree that the}7 are phagocytic. The tissue
F(ETAL NUTRITION: THE PLACENTA 441
around them undergoes fatty degeneration, and in their interior
may be seen remnants of connective tissue and endothelial
cells and fat-globules. Many capillaries are ruptured, and
red and white blood corpuscles are also absorbed. Such an
absorption of maternal tissue by the giant-cells leads
an increase in the size of the implantation cavity and a
thinning of its wall (Disse). In spite of their abundant
supply of nutriment, their life-history is short. No cell-
divisions occur, and soon they degenerate. Their contents are
absorbed by the trophoblast, and their protoplasm shrinks to
form a rim around the nucleus. Later still their remnants
are also absorbed.
The allantois in the mouse is a solid mass of mesoderm with
no entodermal cavity. Growing out from the posterior end of
the embryo, it projects into the extra-embryonic ccelom, and on
the eleventh day fuses with the mesoblast of the ectoplacental
cone. After this the ovum again becomes spherical. The circu-
lation in the decidua reflexa diminishes, and gradually more
and more of the nutriment is conveyed to the embryo by the
allantoic vessels. At the same time the allantoic trophoblast
increases in thickness, and its lacunaa become more numerous
and complicated. Into its mass, in which the circulation of
maternal blood is now established, the vascular mesoblast pro-
jects at intervals, and breaks it up into segments. The glands
take no part in the formation of the placenta. Their ducts do
not even act as guides to the advancing edge of the trophoblast,
as in the rabbit. They are completely displaced by the rapid
formation of decidual tissue, and their remnants are absorbed
by the giant-cells. Hence the embryotrophe contains no
glandular secretion.
At this time the nutritional conditions are essentially the
same as in the rabbit. The trophoblast shows two layers,
plasmodiblast and cytoblast, which intervene, along with
mesoblastic cells and the walls of the villous capillaries, between
the two blood-streams. The subsequent changes are all in the
way of producing an increased surface of contact with maternal
blood, and lessening the thickness of tissue between it and the
foetal circulation.
In the mouse the decidual cells contain glycogen. According
442 THE PHYSIOLOGY OF REPRODUCTION
to Driessen,1 its distribution in the placenta of the white mouse
before mid-term is the same as in the rabbit. It is in great
abundance in the decidual cells, especially in the boundary
layer between the maternal and foetal tissues. No glycogen is
found in the maternal endothelium, or in the fcetal placenta.
Jenkinson 2 has studied the distribution of glycogen throughout
the whole period of gestation in the mouse. It appears first in
the cells which overlie the ectoplacenta, and increases in amount
till the twelfth day, when the mesoblastic processes are just
beginning to project into the trophoblast. Then the decidual
cells are disintegrated and the glycogen granules are mixed
with the detritus. Hence the life-history of the maternal
glycogenic tissue is shorter than in the rabbit. But in the
mouse glycogen again makes its appearance in the trophoblast
which is most directly in contact with the maternal blood,
i.e. the part not penetrated by the allantoic capillaries. It lies
in oblong ectodermal cells, which gradually encroach on and
occupy the space previously occupied by the maternal glyco-
genic cells down to the muscularis. Here the glycogen remains
till the end of gestation.3
According to Kolster, a considerable amount of fat appears
in the decidua, in which the connective tissue and endothelial
cells undergo a fatty degeneration in the proximity of the giant
cells. No observations have been made regarding the meta-
bolism of iron-containing substances.
Guinea-Pig. — In the guinea-pig the ovum is again com-
pletely surrounded by decidua. Reichert 4 was the first to
notice that the ovum lay in a special cavity, " a little nest/'
Bischoff 5 stated that the nest was only temporary, and the
ovum again appeared in the uterine cavity, only that part of the
1 Driessen, " Ueber Glykogen in der Placenta," Arch. f. Gynak.,vol. Ixxxii.,
1907. 2 Jenkinson, loc. cit. See also Brit. Med. Jour., 1904.
3 Whether the differences in the distribution of the placental glycogen
in the rabbit and the mouse during the later stages of pregnancy exist in
reality, or depend only on differences of interpretation, requires further
investigation.
4 Reichert, " Ueber die Bildung der hinfalligen Haute der Gebarmutter,"
Mutter's Arch., 1848.
5 Bischoff, Entwicklung des Meerschweinchens, 1852.
FCETAL NUTRITION: THE PLACENTA 443
nest remaining which formed the placenta. ' After a long interval
this was proved to be wrong by Reichert l and Hensen.2
The fertilised ovum reaches the uterus as a morula or early
blastocyst, surrounded by the zona radiata. On the seventh
day the zona disappears and embedding begins, but even before
this, according to von Spee,3 the ovum is fixed by processes
which extend from the cells of the implantation pole through
the zona and come into direct metabolic relationship with the
epithelial cells. As in the mouse, the blastocyst remains small,
mes
FIG. 107. — Longitudinal section of the uterus and implantation cavity of
the guinea-pig. (From Duval's "Le Placenta des Rongeurs,'' Journ. de
VAnat. etde la Phys., 1892.)
mes, mesometrial border ; gl, uterine glands ; Z, uterine lumen ;
bl, blastodermic vesicle.
about one- tenth of a millimetre in diameter. At its point of
contact with the mucosa, the epithelium is rapidly eroded, and
absorbed along with its fat globules by the foetal ectoderm. At
the same time changes occur in the deeper layers. In the non-
pregnant uterus two layers are present, a sub-epithelial layer of
embryonic connective tissue cells interrupted only by capillaries
and glands, and a deeper, more reticulate layer. Before the
ninth day of pregnancy, no very marked changes occur in the
1 Reichert, "Beitrage zur Entwicklungsgeschichte des Meerschweinchens,"
Abhandl. d. Akad. d. Wissensch. zu Berlin, 1861.
2 Hensen, " Beobachtungen iiber die Befruchtung und Entwicklung des
Kaninchens und Meerschweinchens," Zeit. f. Anat. u. Entwick., vol. i., 1866.
3 Von Spee, " Die Implantation des Meerschweincheneies in die Uterus-
wand," Zeit. f. Morphol. u. Anthropol., vol. hi., 1901.
444 THE PHYSIOLOGY OF REPRODUCTION
mucosa. Some of the cells show mitoses, the blood-vessels are
full, and a few red blood corpuscles may lie between the cells,
and also in the foetal ectoderm. During the penetration of the
epithelium by the trophoblast, some of the superficial connective
tissue cells enlarge. Their nuclei stain more deeply, and the
protoplasm of adjacent cells fuses to form a symplasma. The
degenerated tissue in its immediate neighbourhood is absorbed
^^^^ by the ectoderm, and the
^I^HK blastocyst thus comes to lie
|1 1 1 | in the substance of the mucosa
j I jl (Fig. 107). According to von
Spee, the destruction of uterine
tissue is effected entirely by a
biochemical process ; there is
no evidence of absorption of
formed elements by phagocy-
tosis.
Round the periphery of the
necrotic zone lies a thick layer
of large foetal cells, the two
together forming the " Implan-
tationshof." Later the sym-
plasma degenerates further.
The nuclei shrink and lose
their chromatin, and the proto-
plasm becomes fibrillated and
granular. Vacuolations appear
in the mass, and coalesce to
form a space round the ovum
filled with clear fluid. In this way the implantation cavity is
excavated till it is limited externally by the large cells. Outside it
the decidual cells around the vessels survive, while the rest are
transformed to a symplasma and absorbed. Hence the wall is
sinuous. The dips are, however, filled up in part by newly
formed tissue resembling granulation tissue. It encapsules the
necrotic zone, and may be looked on, as in the rabbit, as a
defence against the advancing ectoderm (see p. 369).
By this time the ovum has become tubular, with its long
axis perpendicular to the long axis of the uterus. It exhibits,
FIG. 108. — Blastodermic vesicle of
the guinea-pig, showing inversion
of the germinal layers. The
blastocyst is tubular, and the
formative cell-mass is invaginated
as in the mouse, but the thickened
trophoblast is not invaginated to
so great an extent as in Fig. 105,
and the connection between them
is lost. Hence the roof of the
amnio-embryonic cavity is inde-
pendent of the trophoblast.
(T. H. Bryce in Quairfs Anatomy,
Longmans.)
FCETAL NUTRITION: THE PLACENTA 445
as in the mouse, an inversion of the germinal layers, but in the
guinea-pig the amnio-embryonic vesicle is closed and separates
the thickened trophoblast from the embryonic ectoderm
(Fig. 108). With the growth of the blastodermic vesicle, the
roof of the implantation cavity projects into the lumen of the~
uterus, and in time obliterates it by coming in contact and
fusing, at the tenth day, with the mesometrial mucosa (Fig. 109).
Here also the cellular tissue has developed at the expense of the
glands, and the surface epithelium disappears. At the fifteenth
mes
FIG. 109. — Implantation cavity of the guinea-pig. (Duval.)
mes, mesometrial border ; I, uterine lumen.
day the lumen reappears anti-mesometrially (Fig. 110). Thus a
secondary decidua reflexa arises which rapidly thins and be-
comes vacuolated in its inner half by a loss of tissue. The cause
of the tissue excavation is uncertain ; it may be brought about
by the large cells which, according to von Spee, are foetal and
form a third layer of the trophoblast outside the plasmodiblast,
and the disintegrated products are probably absorbed by the
ovum. At the same time the vessels which penetrate the
necrotic zone are opened, and blood is effused into the implanta-
tion cavity.
The placenta develops, as in the mouse, mesometrially. The
446 THE PHYSIOLOGY OF REPRODUCTION
allantois consists of a tubular passage in the body wall and a
solid extra-embryonic stalk of mesoderm. It projects into the
ccelom and gradually extends, and becomes applied to the
mesoblast underlying the thickened part of the trophoblast, in
the spaces of which a circulation of maternal blood is established.
The trophoblast continues to attack and absorb maternal tissue
and blood, and to advance more deeply into the decidua, while
at the same time it is penetrated on the embryonic side by out-
mes
am
--- -..*
FIG. 110. — Implantation cavity of the guinea-pig. (Duval.)
mes, mesometrial (placental) border ; I, lumen of uterus, re-established anti-
mesometrially ; d.r., decidua reflexa; all, allantois ; am, amnion.
growths of mesoblast containing branches of the allantoic
vessels. The tissues intervening between the maternal and
foetal blood-streams are entirely fcetal ; they gradually thin
with the progress of gestation and the continued branching of
the mesodermal villi.
Glycogen is contained in the decidual cells, but its variations
have not yet been investigated. It is of interest historically
that oxyhsemoglobin was demonstrated first in the umbilical
vein of a foetal guinea-pig by Schmidt.1 The amounts of oxygen
1 Schmidt, " Sauerstoffhamoglobin in Fotusherzblut," Cent. /. d. med.
Wiss., 1874, No. xlvi.
FCETAL NUTRITION: THE PLACENTA 447
absorbed and carbonic dioxide excreted are the same, weight
for weight, as in the fcetal rabbit (Bohr)^
INSECTIVORA. — The importance ascribed to the placentation
in Insectivora has already been referred to (see p. 377). The"
hedgehog, shrew, mole, and Tupaia have been most fully in-
vestigated.
Hedgehog. — In the hedgehog (Erinaceus europceus), the zona
pellucida disappears early, before the expansion of the hypo-
blast, which, as in Man, forms a closed vesicle. The chronology
of embedding is not yet known. In the earliest stage examined
by Hubrecht,1 the blastocyst was O22 of a millimetre in diameter.
The outer wall was several layers thick all round its circum-
ference, and spaces were already present in it. At a slightly
later stage, the blastocyst grows rapidly and the epiblast is re-
duced to a single layer, with numerous viUiform processes at
intervals, except for a thickened knob which represents the
future germinal area. Even now the name trophoblast may be
given to the single layer of epiblast with its projections, ex-
cluding the thickened knob which is formative and gives rise to
the embryonic ectoderm and the lining of the amniotic cavity.
The mesoblast, as yet one-layered, which extends between the
trophoblast and hypoblast, consists of an attenuated somatic
part which forms with the trophoblast the diplo-trophoblast,2 and
a splanchnic part which forms blood-vessels and blood.
The early blastocyst comes to rest, as in the mouse, in an
anti-mesome trial furrow of the mucosa. It is not yet deter-
mined whether any changes occur previously in the uterus ; but
at least, soon after the blastocyst has taken up its position, there
is a great cell-proliferation in the stroma of the floor and walls
of the furrow, not peri vascular as in the rabbit, but sub-
epithelial. , Along with this decidual formation, the lumina of
the glands are closed, and their epithelium gradually disappears,
perhaps by the influence of the trophoblast. The capillaries
are distended and new vessels are formed. This distension is at
1 Hubrecht, " The Placentation of Erinaceus europceus," Quar. Jour.
Micr. Sci., vol. xxx., 1889.
2 Hubrecht restricts the term chorion to Tarsius (a lemur), monkeys,
apes, and Man.
448 THE PHYSIOLOGY OF REPRODUCTION
first most marked in the lips and sides of the groove, and small
superficial haemorrhages occur, which detach the epithelium at
places. The tissue fluids also exude, and, along with the blood
and desquamated epithelium, form a coagulum around the
ovum. Part of it shuts off the entrance of the furrow from the
uterine cavity.
The epithelium of the crypt, after a preliminary prolifera-
tion such as Robinson describes in the mouse and rat, degenerates
j^* '^.^^^i^^^-.r $ -$f'
||, •M^.^':^j/^ ' ™
:-; •^^'^w , - j&y ^ I- :^ >-^s
• s'. ?*^fe»^ «^.,. V: v*
'^¥^^0' ?WW ' r
s^> ?M/ ^ fe§
T^-^r-*^^— ^vA 'laetoSvi
N.Som.
FIG. 111.— The allantoidean diplo-trophoblast of Erinaceus. (From
Hubrecht's "The Placentation of Erinaceus europceus," Quar. Jour.
Micr. Sti., vol. xxx., 1889.)
Tr.S., trophospongia ; Tr., trophoblast ; F.L., layer of fusiform cells;
Sp., spaces in trophoblast ; M.Som., thin layer of somatic mesoblast.
entirely, part being stripped off by extravasated blood and
part yielding to the influence of the foetal ectoderm. Its
remnants and the other constituents of the coagulum probably
furnish pabulum for the ovum. The development of the de-
cidua proceeds rapidly, and the swollen lips of the groove fuse
together to complete the implantation cavity. The trophoblast is
now in contact with decidual tissue, of which the innermost zone
consists of a stratified layer of fusiform cells, best marked in the
7V.
FCETAL NUTRITION: THE PLACENTA 449
allantoic region (Fig. 111). Whether they are maternal or
foetal in origin is not yet determined. They persist for a time,
but disappear when the endothelial proliferation occurs. Around
the groove, the tissue becomes looser by an increase in the size__
of the newly formed blood-spaces. The endothelium lining
them is swollen and deep, and the cells bulge into the lumen.
Near the ovum the endothelium proliferates and forms an
enormous cell-mass, the trophospongia^ interposed between the
blastocyst and the unaltered decidua. The trophoblast with
its lacunae, and the trophospongia with large blood-sinuses
together form the trophosphere, which, along with the maternal
blood, represents an effective nutritional arrangement for the
embryo before the vitelline or allantoic circulation is estab-
lished (Fig. 112). Many of the blood-spaces are ruptured,
and the blood pours out into the lacunae of the tropho-
blast, and circulates through them before returning into the
maternal veins. At this stage the trophospongia is separated
from the external decidua by rows of fusiform cells.
As in the mouse, in which, however, the trophospongia is
derived from connective tissue cells instead of endothelium,
giant-cells appear. They He between the trophospongia and
the fusiform cells, and they are first seen at the time of the
appearance of the embryonic mesoblast. In their interior are
contained fragments of red blood corpuscles and decidual cells.
Hence they are called deciduofracts by Hubrecht (Fig. 113).
Externally the circular layers of fusiform cells form sheaths
round some of the endothelium-lined vessels. The line of union
between the giant-cells and the external decidua is irregular, and
the decidual tissue is fibrillar and reticulate. These appear-
ances indicate an erosion and absorption of the maternal tissue.
The deciduofracts are probably derived from the maternal
trophospongia (Hubrecht 2). After a short life-history they
dwindle and are themselves absorbed.
1 " The trophospongia is a maternal cell -proliferation specially intended
for the fixation of the blastocyst. It shows a different histological evolution
in different genera " (Hubrecht).
2 Hubrecht now considers that the deciduofracts are of fcetal origin, and
represent the outermost layer of the trophoblast. See p. 470, footnote.
Also compare Graf v. Spec's description of the trophoblast of the guinea-pig
(see p. 444), and Bryce and Teacher's of that of Man (see p. 469).
2P
450 THE PHYSIOLOGY OF REPRODUCTION
With the changes in the mucosa, changes also take place in
the trophoblast. After the thinning already mentioned, its
cells increase in number. They grow in strands, leaving spaces
between them like the meshes of a net, and in the spaces
maternal blood circulates. In this respect the hedgehog differs
Hy. ., ^^ .
Xo/"5^ ' "* ' ' ^' • " "*' ' . .. tf.-sip.
';>i •"" •
Tr. . - v - '
•
*m% #:
+*, \« ,«t«'"
%»*«'
2*»« s/
i
FIG. 112. — Section in «*^ of the ovum of Erinaceus (Hubrecht).
f?t/., hypoblast ; Tr., trophoblast; sp., spaces in the trophoblast, communi-
cating with the maternal blood-spaces (M.Sp.) ; D., decidua ; Trs.,
trophospongia.
from the Rodents, in which the proliferation of the trophoblast
is confined to the allantoic region. In the hedgehog the pro-
liferation occurs even in the omphaloidean region, which is
vascularised by the area vasculosa. Here the vacuolated
trophoblast is gradually interlocked with vascular processes of
the mesoblast, and yolk-villi, containing branches of the vitel-
line vessels, are .developed. The omphaloidean placenta thus
FGETAL NUTRITION: THE PLACENTA 451
formed embraces about one-half of the circumference of the
blastodermic vesicle. With the union of the allantois and diplo-
trophoblast, the circulation in the decidua reflexa decreases,
and it and the trophoblast in contact with it become membra^
naceous. They project into the uterine cavity and obliterate
its lumen by meeting, but not fusing with, the mesometrial
part of the uterine mucosa. As in the bat, the circulation in
the yolk-sac never ceases entirely during pregnancy.
The changes in the allantoidean trophoblast are of the same
Tr- ?™-.... Df.
,s>/. • •
,;v , :;-:{.:;v-.U:^v- *'£ ' ^
FIG. 113. — The extension of the yolk-sac against the lacunar trophoblast in
Erinaceus (Hubrecht). The yolk-sac is to the left of the figure, and its
villi (Vi.) and blood-vessels (B. V.) are well seen.
Tr., trophoblast; Trs., trophospongia; Df., layer of deciduofracts ; D.,
decidua, of which the inner layer (D1) has assumed a more reticulate
aspect; Sp., spaces in trophoblast.
kind, but they occur later. It occupies a discoid area as in
Rodents, but it is on the anti-mesometrial side, i.e. the primary
decidua reflexa is permanent. The lacunar spaces in it are more
complicated than in the omphaloidean trophoblast, and their
walls bulge towards the embryo and interlock with vascular
projections of the allantois. Hence the villi have a complete
trophoblastic covering. The extremity of each villus is attached
to the maternal decidua by strands of trophoblastic cells. The
allantoidean trophospongia develops like the omphaloidean, but
452 THE PHYSIOLOGY OF REPRODUCTION
it retains its thickness later in pregnancy. The deciduofracts
remain distinct to the end, though they partly degenerate. Hence
it is probable that during the whole, or nearly the whole, of
pregnancy they exercise a phagocytic action on the maternal
B. v.
B.V
FIG. 114. — Transverse section through the uterus of Sorex at a stage when
the blastocysts are still in the oviducts. The coiled uterine glands (Gl.)
are massed together in the anti-raesometrial regions. The uterine lumen
(U) is more or less _|_-shaped. (From Hubrecht's "The Placentation of
the Shrew," Quar. Jour. Micr. Sci., vol. xxxv., 1894.)
B. V., blood-vessels ; c.m., circular muscle ; l.m., longitudinal muscle.
tissues, and store nutriment which they give up to the embryo
in a way as yet unknown.
Shrew. — In the shrew (Hubrecht l) the method of embedding
is centric, and no decidua reflexa is formed. The yolk-sac pla-
centa is not so well developed as in the hedgehog.
The attachment of the blastocyst is modified, as in Ruminants,
1 Hubrecht, " The Placentation of the Shrew," Quar. Jour. Micr. Sci.,
vol. xxxv., 1894.
FGETAL NUTRITION: THE PLACENTA 453
by special characteristics of the uterine mucosa. They differ
from the cotyledonary burrs, however, in being proliferations
of the surface epithelium. Before the fertilised ova reach the
uterus, there are variations in thickness in the mucosa. It is
thin at the mesometrial and anti-mesometrial sections, but~
thickened over the sides to form two cushions, in which the
blood-vessels are more numerous. No glands are present near
the mesometrium. They are collected on the opposite surface
and open into a longitudinal anti-mesometrial groove (Fig. 114).
U.E.
FIG. 115. — Part of the anti-mesometrial wall of the uterus of Sorex
(Hubrecht). The proliferated epithelium is arranged in a radial fashion,
and later it forms a secondary crypt (Cr.), when the uterine epithelium
(U.E.) gives way over it.
When the blastocysts reach the uterus, further changes
take place. Both the lateral regions increase in thickness by the
proliferation of connective tissue cells and the formation of new
vessels, while the anti-mesometrial part is widened out into a
concave bell-shaped surface into which the glands open. Then
the epithelium proliferates, first in the lateral cushions and
later in the concave area. In the former the proliferation
reaches a thickness of twelve to eighteen cells, and the new
elements pass in among the cells and vessels of the deeper
layers. In the allantoidean region, the bell-shaped area, the
proliferation also leads to a thick epithelial layer with vascular
channels between the cells. At intervals, however, the cells are
454 THE PHYSIOLOGY OF REPRODUCTION
arranged radially like a fan, and later the internal parts of the
cells break away and leave a crypt. No crypts are formed in the
lateral cushions (Fig. 115).
Over the special areas of the mucosa the trophoblast thickens.
It comes in contact first with the lateral cushions by a zonary
strip against which the vessels of the area vasculosa spread out.
The cell-outlines in the epithelium of the cushions are lost, and
a symplasma is formed. At the same time the trophoblast be-
comes syncytial, is fused to the uterine symplasma, and absorbs
part of it. Some of the intercellular channels are opened, and
the maternal blood thus begins to circulate in the syncytial
lacunae. At the same time a deeper cell layer, corresponding to
the cytoblast of the bat, appears in the trophoblast, but it is
never so well marked as in the allantoidean region. In this
way the avillous yolk-sac placenta is formed (see also p. 391),
and it functions for a time. Soon retrogressive changes appear,
resulting in the absorption of the omphaloidean syncytium and
epithelial thickenings (Fig. 116). The disappearance is ap-
parently brought about by a newly formed annular proliferation
of the trophoblast above the non-placental part, and the de-
generated products of the thickened uterine epithelium and of
a blood extra vasate, which constantly exists between the annulus
and the epithelium, are absorbed and transmitted through the
hypoblast to the yolk-sac. From it the vessels of the area
vasculosa, which at this time reach their full development,
carry the nutriment to the developing embryo.
The allantoidean trophoblast is applied against the bell-
shaped proliferation on the anti-mesometrial side of the uterus,
and is fixed by projections which sink into the newly formed
crypts. After destroying their epithelial lining, the projections
erode capillaries, and the maternal blood circulates in the
syncytial lacunas as in the omphaloidean trophoblast. The
cytoblast follows the plasmodial projections, and later the
trophoblastic villi are vascularised by the allantoic vessels.
Subsequently the plasmodiblast thickens to a considerable
extent, and in it the mesoblastic villi continue to branch and
form secondary and tertiary villi. There is no penetration on
their part into the decidual tissue between the crypts, but the
maternal part of the placenta as a whole is gradually absorbed
FCETAL NUTRITION: THE PLACENTA 455
by the plasmodiblast, and is replaced by foetal elements. In the
ripe placenta the only maternal constituent is blood, except a
Cr.
np.T
FIG. 116. — Uterus and embryo of Sorex (Hubrecht).
a.T. , allantoidean trophoblast with knobs entering the epithelial crypts (Cr.) ;
am., amnion ; all., free knob projecting into the extra- embryonic ccelom
(E.ec.) ; a.v., area vasculosa ; an', embryonic cells which grow downwards
from the upper rim of the trophoblastic annulus (tr.an.), and adhere
against the maternal tissue; np.T., non-placental trophoblast; Gl.t
glands ; M., mesometrium.
thin discoid sheet of nuclear remnants next the muscularis. The
glands are not penetrated by vascular vim. In the early stages
they are plugged by syncytium and later disappear.
456 THE PHYSIOLOGY OF REPRODUCTION
Mole. — The method of embedding is centric. A simple
yolk-sac placenta exists for a time. The allantoic placenta is
discoid and is placed anti-mesometrially. The glandular secretion
is of importance for the nourishment of the developing foetus
during the greater part of pregnancy (Strahl,1 Vernhout 2).
At the beginning of pregnancy the mucosa shows variations
in its different parts. Near the mesometrium, for about one-
third of the circumference of the lumen, the glandular layer is
thin. Anti-mesometrially the muscular layer is not so well
developed, but superficially to the glands there is a proliferation
of connective tissue cells, through which the ducts run to open
into the lumen. The first attachment is in this region.
The uterine horns show a series of small swellings where the
ova are present. The blastocysts grow to a comparatively
large size, and completely fill up the lumen. By their further
growth, the epithelium near the mesometrium is flattened and
replaced by trophoblastic cells, which do not penetrate into the
connective tissue or form villi. Hence the yolk-sac placenta is
is of a simple type ; it persists throughout pregnancy.
On the opposite side the decidual formation proceeds, and
the mucosa becomes thicker. In its substance a rich network
of blood-capillaries is developed. The epithelial cells lose their
boundaries and form a symplasma. According to Strahl this
remains, and forms the syncytial covering of the future villi, but
Vernhout has shown that the trophoblast proliferates and forms
a layer of epithelioid cells which penetrate into the epithelium
and absorb and gradually replace it. Over each gland-opening
the trophoblast forms a dome as in Ruminants (Fig. 117). In
the placental region the glandular epithelium is not changed,
and around each opening a small area of the surrounding
uterine epithelium persists. In the cavity between a gland-orifice
and its trophoblastic cap lies a dark secretion, pigmented by
admixture with extravasated blood, and the cap is similarly
pigmented. Hence the secretion is probably absorbed by the
foetal ectoderm throughout the greater part of pregnancy during
which the glands remain. After the disappearance of the surface
1 Strahl, " Ueber den Bau der Placenta von Talpa europea" Anat. Anz.,
vol. v., 1890.
2 Vernhout, " Ueber die Placenta des Maulwurfs," Anat. Hefte, vol. v.,1894.
FCETAL NUTRITION: THE PLACENTA 457
epithelium at the point of connection with the blastocyst, the
plasmodiblast penetrates into the connective tissue layer which
forms a symplasma. It is followed by the cytoblast and the
allantoic villi. In the syncytium the circulating maternal
,.'
FIG. 117. — Orifice of a uterine gland of the mole with trophoblastic dome.
(From Vernhout's "Ueber die Placenta des Maulwurfs," Anat. Hefte,
vol. v., 1894.)
m., uterine mucous membrane ; ue., uterine epithelium ; pi., plasmodiblast ;
c2/-> cytoblast ; g.s. , gland secretion.
blood provides for the exchange of gases, and supplements the
nutriment supplied by the glandular secretion.
Tupaia. — In Tupaia javanica also, the placentation is modi-
fied by the characteristics of the uterine mucosa. Hubrecht x
1 Hubrecht, " Ueber die Entwicklung der Placenta von Tarslus und
Tupaja" Internat. Congr. of ZooL, Cambridge, 1898.
458 THE PHYSIOLOGY OF REPRODUCTION
has shown that two specialised areas, the " Haftflecke,"
exist before the attachment of the trophoblast. They lie
one on each side, about midway between the mesome trial
and an ti-mesome trial regions, and are recognised by the ab-
sence of glandular ducts. The deeper parts of the glands
persist till the end of pregnancy, but none open on the modified
areas.
The uterine epithelium again disappears at the points of
contact with the blastocyst over the " Haftflecke." There the
trophoblast becomes thickened, and its cells enlarge and pene-
trate between the epithelial cells, which fuse to form a sym-
plasma. This is quickly absorbed by the trophoblast, which
continues to thicken, and now shows two layers, plasmodiblast
and cytoblast. The outer layer fuses so closely with the de-
cidual tissue as to be indistinguishable from it. The capillaries
dilate and new vessels are formed, especially in the layers next
the ovum. When their endothelium is destroyed, maternal
blood enters the trophoblastic lacunae and soon circulates
through them. The inter- vascular connective tissue cells pro-
liferate and form the trophospongia. The decidual layers
outside it become fibrillar, and soon are extremely attenuated.
The trophospongia remains longer, but finally it also thins,
and at the end of pregnancy there is only a thin rim of maternal
tissue left.
Over the " Haftflecke " the trophoblast is first vascularised
by the vitelline vessels, and a temporary yolk-sac placenta is
formed. Later the allantois displaces the yolk-sac, and its
vessels vascularise the same part of the trophoblast (Fig. 118).
" The permanent placenta replaces the omphalic placenta both
physiologically and topographically " (Hubrecht). In this respect
Tupaia differs from the hedgehog and the shrew.
Centetes. — A peculiar form of placentation has been de-
scribed by Strahl1 in the tenrec (Centetes ecaudatus). A large
effusion of maternal blood destroys the centre of the allantoic
placenta, and leaves only a peripheral ring. Round the margin
1 Strabl, "Beitrage zur vergleichenden Anatomie der Placenta," Abh.
Senckenberg Naturf.-Ges., 1905. See also Kolleston, "On the Placental
Structures of the Tenrec (Centetes ecaudatus}" &c., Trans. Zool. Soc., London,
vol. v., 1863.
FCETAL NUTRITION: THE PLACENTA 459
of the ring runs a deep groove which is crossed by branches of
the allantoic vessels to reach an epithelial ridge of cells.
CHEIROPTERA. — The mode of embedding in the bat is centric,
and the allantoic placenta is discoid. Before segmentation is
completed, the fertilised ovum reaches the uterus and invariably
enters the right cornu (Ercolani *). The zona pellucida is
already thinned and soon disappears, the spherical blastodermic
vesicle lying free in the uterine cavity.
At the beginning of gestation, according to van Beneden,2
All.
FIG. 118. — Replacement of omphaloidean by allantoidean placenta in Tupaia.
(From Hubrecht's " Ueber die Entwicklung der Placenta von Tarsius
und Tupaja" Internal. Congr. of Zool., Cambridge, 1898.)
m.v., mesodermic villi ; Tr., trophoblast ; Ta. , trophospongia ; All., allantois ;
2/.5., yolk-sac.
the mucosa is composed of a richly cellular connective tissue,
covered by a non-ciliated epithelium. Of the glands some are
simple tubes, and others divide dichotomously. None open on
the mesometrial aspect where the blastocyst later becomes
fixed. There also the cellular tissue is not so thick.
Before fixation of the blastocyst, important changes occur
1 Ercolani, " Nuove ricerche sulla placenta nei pesci cartilaginosi e nei
mammiferi," Mem. deW Accad. d. Sc. dell' Institut. di Bologna, vol. x., 1879.
2 V. Beneden, " De la formation et de la constitution du placenta chez
le murin," Oomp. Rend, de la Soc. de Biol., vol. v., 1888.
460 THE PHYSIOLOGY OF REPRODUCTION
in the mucosa. The sub-epithelial connective tissue cells pro-
liferate and form a distinct compact zone. All the capillaries
dilate, even before the disappearance of the zona pellucida, and
give off many new branches. The tissue fluids are increased,
and a serous fluid is transuded and forms, with the glandular
secretion, a coagulum around the ovum (Van der Stricht l).
On the mesome trial side, the trophoblast thickens around
the formative cell mass, and absorbs the surface epithelium.
At the opposite pole the cells are flattened, and they also dis-
appear. The foetal ectoderm, which thus comes in contact
with the connective tissue, is composed of two layers at the
embryonic pole, the plasmodiblast, and, internally to it, the
cytoblast. At the non-embryonic or anti-mesometrial pole
the plasmodiblast is absent.
The decidua also differs at the two poles. Opposite the
non-embryonic pole, the cells remain epithelioid and undergo
little change. Where they come in contact with the tropho-
blast, they show a tendency to necrose. At the placental pole
the deeper layers are also composed of epithelioid cells, but
superficially the. capillaries continue to dilate and make the
layer spongy. The cells between them are in active division,
but next the plasmodiblast they degenerate. This layer forms
the couche paraplacentaire of Nolf 2 (Fig. 119). At the placental
margin it thins out and disappears. Beneath the epithelioid
layer in both areas the cells are drawn out and pseudo-fibrous.
The conditions for nutrition resemble those in the very early
human ovum, the trophoblast lying against a non-vascular
detritus-zone. But in the bat there is strong evidence of
phagocytosis. The epiblastic protoplasm, where it is in contact
with dead tissue, is " crammed with irregular granules, some
fatty and others coloured brown with safranin " (Nolf). The
mouths of the glands opening at the non-embryonic pole are
filled with debris, and their epithelium is degenerated and
desquamated. As previously mentioned, no gland-ducts are
present in the couche paraplacentaire. The blind ends of the
1 Van der Stricht, "La fixation de 1'oeuf de chauve-souris h, 1'interieur
de 1'uterus," Verh. d. anat. Gesell., 13 Vers., Tubingen, 1899.
2 Nolf, "Etude des modifications de la muqueuse uterine pendant la
gestation chez le murin," Arch, de Biol., vol. xiv., 1896.
FOETAL NUTRITION: THE PLACENTA 461
glands are, however, distended with secretion, and their
epithelium is normal.
Next a change occurs such as Hubrecht described in the
hedgehog (see p. 449). The endothelium of some of the vessels
in the paraplacental layer proliferates irregularly round the
-Art
FIG. 119.— The placenta of the bat. (From Nolf's " Etude des modifications
de la muqueuse uterine pendant la gestation chez le murin," Arch, de
BioL, vol. xiv., 1896.)
m., muscularis ; a., unaltered mucosa ; C.ep., epithelial layer; gl., glands;
C.pp., paraplacental layer with blood-spaces (6.) ; Art., artery running
towards trophoblast ; Ve., vein ; Tr., trophoblast with lacunae ; Vil. all.,
allantoic villi.
lumen, and degenerates. In the bat, according to Nolf, the
vessels in which the change occurs are the venous capillaries, in
which the blood, returning from the placenta charged with
foetal excretory products, stagnates and produces the hyper-
plasia and simultaneous degeneration. Hubrecht, however,
462 THE PHYSIOLOGY OF REPRODUCTION
states that an endothelial proliferation occurs in arterial and
venous capillaries alike in the hedgehog.
At the embryonic pole the plasmodiblast undergoes a
marked thickening. It gradually replaces the superficial de-
cidual cells, and surrounds the vessels as in the rabbit. Then it
attacks the endothelial sheath and replaces it, so that lacunae of
maternal blood come to be surrounded by foetal tissue. At the
same time the cytoblast sends out cellular buds, which project
into the plasmodial mass. Under the cytoblast is the double
layer of mesoblast, the thin somatopleur, and the splanchno-
pleur in which the area vasculosa is developed. A yolk-sac
placenta is thus formed in the same region as is subsequently
occupied by the allantoic placenta. Nutritive exchanges be-
tween maternal and foetal blood are now possible.
In the further development of the placenta there is very
little or no penetration of maternal tissue by the trophoblast
(Duval *). Degenerative changes occur in the cells of the
epithelioid layer in the placental hemisphere. They lose their
outlines, and form a symplasma which is absorbed by the ad-
jacent cells of the couche paraplacentaire (Nolf). Superficially
the paraplacental layer remains until the end of pregnancy.
The blind ends of the glands are still distended, but their
epithelium degenerates and is cast off into the lumen.
In the non-placental trophoblast, retrogressive changes also
occur. Its cells lose their phagocytic power and contain no
granules. In the placental area, as already mentioned, the
allantois replaces the yolk-sac. The " villi " resemble the tubes
of the rabbit. They form a series of arches whose meshes
are occupied by allantoic vessels ; there are no villi hanging
free. As the placenta develops, the thickness of the arches sur-
rounding maternal blood is reduced, and the two blood-streams
lie close together. The cytoblast almost entirely disappears.
Pteropus edulis. — In Pteropus the placenta is attached to a
large mushroom-shaped outgrowth of the uterine wall which
grows nearly round the ovum to form a decidua capsularis. As
pregnancy advances, the outer wall of the bell-shaped decidual
1 Duval, " ]£tude sur I'embryologie des Cheiropteres," Journ. de I'Anat.
etdelaPhys., 1895-97.
FCETAL NUTRITION: THE PLACENTA 463
mass is pressed against the uterine surface and fuses with it.
In this way the completed placenta is discoid (Gohre *).
PRIMATES. — The order of the Primates includes monkeys,
apes, and Man. Hubrecht also includes Tarsius, a lemur (see"
p. 410). Owing to the difficulties of securing material for
investigation, many details regarding the early stages of
development of the foetal membranes and placenta are yet
unknown.
From the researches of Turner, it is known that the placenta-
tion is in general the same throughout the order, except for
differences in the size and form of the villi, and in the structure
of the decidua. On the other hand, the Primates are distin-
guished from all other placental Mammals in that they do not
form an allantoic placenta. Notwithstanding the variations
in the degree of its development, in all the orders previously
considered the allantois projected free into the extra-embryonic
ccelom before it was united with the wall of the blastodermic
vesicle. In the Primates and Tarsius the embryo is attached
from the beginning to the wall of the blastocyst by the " Bauch-
stiel " or " Haftstiel," a mesodermal connecting-stalk first ob-
served by His 2 in human embryos. The allantois appears very
early as a recess of the posterior wall of the yolk-sac before the
formation of the hind-gut. It never projects free into the
ccelom, but is contained as a narrow tube in the " Bauchstiel "
without reaching at any time the wall of the blastocyst (Fig. 120).
The trophoblast is in this way vascularised directly, and a
chorionic instead of an allantoic placenta is formed. For this
reason Hubrecht has suggested that the term chorion should be
restricted to the Primates. Minot 3 strongly supported the views
of His. He went even further, and stated that the placenta was
also chorionic in Carnivora, Rodentia, Insectivora, and Cheirop-
tera, but his views have not been generally accepted. Re-
garding the modification in Primates, Hubrecht 4 says : " Once
1 Gohre, " Dottersack und Placenta des Kalong (Pteropus edulis}"
Studien uber Entwicklungsgeschichte der Thiere, Selenka, vol. v., 1892.
2 His, Anatomie menschlicher Embryonen, I.
3 Minot, Human Embryology, Boston, 1892.
4 See Robinson's " Hunterian Lectures," Journ. of Anat. and Phys.,
vol. xxxviii., 1904.
464 THE PHYSIOLOGY OF REPRODUCTION
the embryonic circulation has found the shortest route towards
the trophoblast by way of the ' ventral stalk/ trophoblastic
lacunae, with their profusion of maternal blood, which have
been there from the very earliest periods of development, are
exquisitely situated for rendering this new adaptation highly
advantageous. And while in the ancestral forms of the Primates
both yolk-sac and allantois largely drew upon the trophoblastic
source, these embryonic organs come to be dispensed with to a
very great extent in their more highly developed descendants
who come to use that trophoblastic source along a more direct,
a shorter, and an earlier established route/'
~ch.
FIG. 120. — Median longitudinal section of an early human ovum, 0'4 mm. in
length. (From Quain's Anatomy, Longmans. )
e.ec., embryonic ectoderm ; ch., chorion ; ec., ectoderm ; mes., mesoderm ;
all., allantois ; c.s., connecting stalk ; a., amnion ; y.s., yolk-sac.
In old-world monkeys there is no decidua capsularis. The
trophoblast thickens over two discoid areas on the blastocyst,
and the thickenings form a primary placenta on the dorsal
surface, and a smaller secondary placenta on the opposite
aspect. Hence two groups of chorionic villi are developed.
No unattached blastocyst has yet been obtained. In the
youngest specimen of an old-world monkey, Semnopithecus
nasicus, the ovum was attached to the surface of the uterus
by large villous processes with mesoblastic cores at the bases.
The trophoblast consisted of two layers, the cytoblast, which
was much thickened at the tips of the mesoblastic cores, and,
externally to it, a syncytium which was blended at the apices
with maternal decidua. Over the non- villous chorion, syncytium
FCETAL NUTRITION: THE PLACENTA 465
was" absent (Selenka). Spaces, which are in direct com-
munication with maternal capillaries, are present in the
syncytium. The most notable characteristic in the decidua is
the presence of a glandular secretion in the embryo trophe. In
the non-placental area the glands are dilated and open into the"
uterine cavity, many of them close to the peripheral villi.
Hence their secretion may reach the trophoblastic lacunae. In
the placental region they are also dilated, but their superficial
parts are closed and appear to degenerate early. In the decidua
lie nests of epithelioid cells, the origin of which is uncertain.
The new-world monkeys, like the old-world, have no de-
cidua capsularis, and the placenta is formed as a single disc.
In the anthropoid apes, on the other hand, the ovum is lodged
in an implantation cavity, and so is covered by a reflexa. The
whole circumference of the trophoblast thickens and develops
villi, but later they disappear except over a discoid area, the
decidua serotina. In the earlier stages two main groups of
villi are present, as in the old-world monkeys, while the rest of
the chorion is covered with smaller villi.
In Selenka's youngest specimen, the ovum was completely
enclosed by decidual tissue, and there was no evidence to show
whether the mode of embedding was excentric or interstitial.
The surface of the ovum was separated from the decidua by a
series of intercommunicating spaces, the intervillous spaces,
which contained lymph. In other words, Selenka looks on the
intervillous space in apes as a space lying between maternal
and foetal tissues, in which villi are suspended.
In Man also the villi are at first diffuse, and later restricted
to a discoid area, the placenta being again developed in the
decidua serotina.
The ovum probably reaches the uterus still enclosed in the
zona pellucida, and lies free until the end of the first week, but
this stage has never been observed. The uterine mucosa, as in
other orders, is matured about the time of puberty (Bjorken-
heim 1), and then consists of embryonic connective tissue cells,
separated from the surface epithelium by a layer of flattened
cells. The intercellular spaces are filled with lymph, and they
1 Bjorkenheim, " Zur Kenntnis der Schleimhaut im Uterovaginalkanal
des Weibes in den verschiedenen Altersperioden," Anat. Hefte, H. cv., 1907.
2G
466 THE PHYSIOLOGY OF REPRODUCTION
drain into lymphatic vessels in the outer half of the mucosa,
where also the arterioles and venules lie. All the blood-vessels
in the inner half are capillaries. In all probability the fertilised
ovum, during its sojourn in the Fallopian tube and while it lies
free in the uterine cavity, does not influence the structure of
the mucosa, and may implant itself at any period during the
cestrous cycle (Bryce and Teacher l). But under the abnormal
conditions in a tubal pregnancy, the uterine mucosa undergoes
a decidual change although no fertilised ovum is embedded in it.
In all the early specimens the ovum was completely en-
closed in the uterine mucosa, and the actual process of em-
bedding has not yet been observed. John Hunter considered
that the ovum reached the uterus from the Fallopian tube under
the mucous membrane, and so had a decidua reflexa, while at a
later stage the mucosa developed underneath it ; hence the
term decidua serotina. Sharpey supposed that the enclosure
was effected by circumvallation, i.e. by a growth round the
ovum of two folds of mucosal tissue, which fused and formed
the decidua capsularis. But v. Spee 2 discovered a different
mode of embedding in the guinea-pig, and later stated that it
was the same in Man, viz. a destruction of the superficial
epithelium, and the implantation of the ovum in the cellular
substance of the mucous membrane. This view has received
considerable support from the researches of v. Heukelom,3
Peters,4 Bryce and Teacher, and others. At the same time
it must be borne in mind that His,5 in describing an early
human ovum in 1897, stated that the implantation cavity was
lined with epithelium, and thus represented a part of the
uterine lumen shut off by the growth of decidual folds.
At the time of embedding, segmentation has probably
1 Bryce and Teacher, The Early Imbedding and Development of the
Human Ovum, Glasgow, 1908.
2 V. Spee, "Neue Beobachtungen iiber sehr f riihe Entwicklungsstufen des
menschlichen Eies," Arch. f. Anat. u. Phys., anat. Abth., 1896.
3 V. Heukelom, " Ueber die menschliche Placentation," Arch. f. Anat.
u. Phys., anat. Abth., 1898.
4 Peters, Ueber die Einbettung des menschlichen Eies, Leipzig u. Wien,
1899.
5 His, "Die Umschliessung des menschlichen Frucht wahrend der
friihesten Zeit der Schwangerschaft," Arch. f. Anat. u. Phys., anat. Abth.,
1897.
FCETAL NUTRITION: THE PLACENTA 467
finished and the ovum is in the condition of the early blastocyst.
Its epiblastic wall disintegrates the epithelium, the subjacent
cells, and a few capillaries at the point of contact. Hence the
blastocyst comes to lie in the connective tissue of the mucosa,
which completely surrounds it, except at the point of entrance of
the ovum. Here there is a gap in the tissue, the " Gewebspilz/'
filled up at first by a blood-clot which afterwards becomes
fibrinous (Peters), and later by decidual tissue (Kollmann *).
In Peters' ovum the gap was four-fifths of a millimetre in
diameter, and in Bryce and Teacher's a tenth of a millimetre.
The size of the ovum when it becomes embedded is probably,
according to the last-named authors, a fifth of a millimetre.
When the hypoblast of the early blastocyst is differentiated,
it does not apparently line the wall of the blastocyst, but forms
a small vesicle. Very early, even- before the appearance of the
primitive streak, a marked proliferation of mesoblast occurs
(Fig. 121). In the youngest ovum its cells filled the space
between the wall of the blastocyst and the small amniotic and
hypoblastic vesicles. In the ovum described by Leopold,2 it was
already split by the " Haftstiel " into two parts, which enclosed
the ccelom and were continuous with each other (Fig. 122). The
outer wall of the blastocyst, the foetal ectoderm or trophoblast
which anchors the ovum in the mucosa, is thickened all round
its circumference, and even in the earliest specimen contained
vacuoles into some of which maternal blood had penetrated. In
this thick spongy layer Bryce and Teacher found no cell-outlines
anywhere. Hence the transformation to syncytium is not due, as
Peters supposed, to the contact with maternal blood. Under the
syncytium is the ceUular layer, corresponding to the cytoblast of
Beneden. Its cells are in a state of active division, and they
appear later to lose their outlines and merge into the syncytium.
The growth of the latter from the mother-zone of cytoblast occurs,
not as a solid mass, but in strands forming primitive syncytial
villi (Fig. 123). Into the syncytium project outgrowths of the
cytoblast, forming the cellular villi of Peters and Leopold. In the
1 Kollmann, "Die menschlichen Eier von 6 Millimeter Grosse," Arch,
f. Anat, u. Phys., anat. Abth., 1879.
2 Leopold, " Demonstration eines sehr jungen menschlichen Eies," Arbeiten
aus d. Konigl. Frauenklinik in Dresden, Leipzig, 1906.
468 THE PHYSIOLOGY OF REPRODUCTION
youngest ovum the formation of these buds was just commencing,
and, according to Bryce and Teacher, they tended to grow out
not so much into the strands of trophoblast as into the spaces
6 •§
between them. Later still, mesoblastic processes penetrate into
the cellular buds and complete the vascular chorionic villi.
Round the blastodermic vesicle is a zone of degenerated tissue,
the " Detrituszone " (Fig. 124). It is uncertain whether it is
formed by the influence of the trophoblast or maternal elements.
FOETAL NUTRITION: THE PLACENTA 469
At its inner edge, and within its spaces, are numerous large
mononuclear cells which are " more likely maternal " (Bryce and
ki
<u a "e
111
xj a
^ 2
Teacher). Peters also mentioned the presence of many large
cells, and compared them to the deciduofracts of the hedgehog.
470 THE PHYSIOLOGY OF REPRODUCTION
V. Heukelom described the cellular layer outside the syncytium
as foetal, and derived from Langhans' layer.1 Whatever their
• • * .. ::
% » *».*,»
j *
— dec
—end
%,^©»
* * • »*
.^w
FIG. 123. — Section of a portion of the wall of the human blastocyst.
(Bryce and Teacher.)
cyt., cyto-trophoblast ; dec., decidua ; end., endothelium of maternal capillary ;
pi., plasmodium ; nz., necrotic zone of decidua.
1 Much uncertainty still exists regarding the origin of these large cells
in Man and other animals. In the mouse, Duval and Sobotta consider them
foatal, Kolster and Disse maternal, and Jenkinson both foetal and maternal.
In the guinea-pig, v. Spec states that they are foetal. In the hedgehog
they were first described by Hubrecht as maternal, and later as foetal. In
Man, as stated above, the same doubt exists whether the trophoblast con-
sists of two layers, cytoblast and plasmodiblast, or possesses a third layer
composed of large cells, and forming the advance guard in attacking the
uterine mucous membrane and enlarging the " Eikammer."
FCETAL NUTRITION: THE PLACENTA 471
origin, the mononuclear cells in Man appear to be engaged in
disintegrating mucosal tissue, and producing a zone of coagula-
tion necrosis, i.e. a symplasma, around the trophoblast. But
they differ from similarly situated cells in lower animals, e.g.
the mouse, in showing no evidence of ingestion of formed tissue-
elements.
me —
FIG. 124.— Section of a portion of the necrotic zone of the decidua, and of
the layer of large cells on its inner aspect. (Bryce and Teacher.)
wz., necrotic zone ; me., large cells in various stages of degeneration ;
cav.> blood-filled implantation cavity.
In the youngest ova no space exists between the trophoblast
and the wall of the implantation cavity (Fig. 125). In later
specimens a space is formed, apparently by the absorption of the
debris of the necrotic zone. How this excavation is brought
about is uncertain. According to Peters, the trophoblast may
exercise a phagocytic action. Bryce and Teacher, however, found
472 THE PHYSIOLOGY OF REPRODUCTION
no evidence of such a process, and inclined to the opinion that
the material was dissolved by an enzyme before its absorption.
In the trophoblast they found that some of the vacuoles were
not yet filled with maternal blood, but contained a granular
coagulum which might, when liberated, have a digestive activity.
In either case, the extensive proliferation of the trophoblast
FlG. 125. — Section through embryonic region of ovum (after Peters).
(From C. Webster's Human Placentation.)
E.Sch., embryonic epiblast ; Ent., embryonic hypoblast ; Mes., mesoblast ;
D.S., umbilical vesicle ; A.H., amniotic cavity ; Ekt., chorionic -epiblast ;
Sp., space.
appears to provide for the absorption of the necrosed tissue
around it, as well as for the flow of maternal blood into its
lacunae by the erosion of superficial capillaries. These two
objects accomplished, the greater part of the trophoblastic pro-
liferation disappears.
Immediately after the excavation of the cavity the decidual
formation begins. Before this stage, the changes resemble those
that take place during the menstrual period. The vessels are
FOETAL NUTRITION: THE PLACENTA 473
dilated, and blood extravasations occur between the cells and
into the lumen. The tissue is
cedematous and spongy, and
the swollen cells often appear
to be floating free in a fluid
(v. Heukelom). These changes
are especially marked near the
ovum, and they give rise to
an elevation which marks
the resting-place of an early
blastocyst. The mucosa is
differentiated into a superficial
layer, the compacta, and a
deeper layer, the spongiosa, in
which are the enlarged middle
portions of the glands, arterioles,
venules, and lymphatics. In
the compacta the connective
tissue cells undergo active
division, and they enlarge to
form the decidual cells (Fig.
126). Before the excavation
of the " Eikammer " they are
probably not found, though
Peters described the com-
mencement of a decidual
change before that stage. In
Merttens' 1 ovum large decidual
cells were found, many of them
fusiform and lying parallel to
the surface. The decidual
change arises first in the
connective tissue cells near
the ovum, and later it ex-
tends more deeply in the
FIG. 126.— Condition of the glands
at the beginning of pregnancy in
Man (after Kundrat and Engel-
mann). (From Quain's Anatomy,
Longmans.)
c, compact layer near free surface of
decidua: the glands are here some-
what enlarged, but not very tor-
tuous, and the mucous membrane
is rendered compact by the hyper-
trophy of the interglandular tissue;
sp., spongy layer containing the
m iddle portion of the glands greatly
enlarged and tortuous, producing
a spongy condition in the mucous
membrane ; d, deepest portion of
glands, elongated and t ortuous.but
not much enlarged ; m. , muscularis.
compacta. There is no special perivascular development as
1 Merttens, " Beitrage zur normalen und pathologischen Anatomic der
menschlichen Placenta," Zeitschr. /. Geburtsh.u. Gynak., vols. xxx. andxxxi.,
1894-5.
474 THE PHYSIOLOGY OF REPRODUCTION
in the rabbit, and no endothelial proliferation as in the hedge-
hog and bat, though the latter may occasionally occur in
tubal pregnancy (Webster 1).
The capillaries dilate to sinuses, and new vessels are also
formed in the compacta. Many of them are opened by the
trophoblast and perhaps by the mononuclear cells, and gradually
more and more blood is effused into the trophoblastic lacunae.
In them it does not clot, the syncytium acting as an endothelium,
but at a certain stage the blood begins to circulate and continues
to do so throughout pregnancy. The gland-ducts are destroyed
in the necrotic zone. In the underlying compact zone they are
found dilated in the serotina and base of the reflexa, but even
in Bryce and Teacher's ovum the epithelium showed signs of
degeneration and desquamation.
With the formation of the space between the ovum and the
decidua, a permanent attachment of the two structures is
brought about. The development of the villi has already been
traced up to the stage when they consisted of simple stalks of
mesoblast with a double ectodermal covering. In the core are
developed capillary vessels which are continuous with the vessels
of the " Haftstiel," and later with those of the umbilical cord.
After the excavation of the necrotic zone, some of the stalks
reach the decidual surface and attach the ovum to it. At first
the attached ends of these primary villi are plasmodial, but
later the cytoblast proliferates and forms thick rounded masses,
the " Zellsaulen," over which the syncytium disappears. This
forms the permanent attachment between the villi and the de-
cidual surface. The spaces between the stalks form the primary
intervillous space, which is thus entirely in the plasmodiblast.
The primary villi form buds of their three layers which develop
into secondary villi. Of these some may also become attached
to the decidua, while others hang free in the intervillous space.
By a similar process other villi are also developed, till the whole
system becomes branched like a tree (Fig. 127). At first they
are equally distributed over the chorion, but the villi in relation
to the reflexa do not branch so much, and even at the end of the
1 Webster, Human Placentation, Chicago, 1901. Wade and Watson
(Journ. of Obstet. and Gynec. of Brit. Emp., 1908) also state that in tubal
pregnancy some of the decidual cells are formed from endothelium.
FCETAL NUTRITION: THE PLACENTA 475
first month they are fewer in number than over the serotina
(Kastschenko *). When the blood-supply to the reflexa is re-
duced, the villi in relation to it degenerate, and are compressed
between the chorion and the apposed decidua reflexa and vera.
Over the serotina they continue to branch and form the fcetah~
FIG. 127.— Median longitudinal section of an embryo of 2 mm. (von Spec).
(From Quain's Anatomy, Longmans.)
v., villus ; c.v., core of villus ; mes., mesoderm ; c.s., connecting stalk; p.s.,
primitive streak; all., allantois ; y.s., yolk-sac; Ent., entoderm ; ves.,
vessels; h., heart ; n.p., notochordal plate ; a., amnion.
part of the placenta, which is essentially a mass of foetal villi
between which maternal blood circulates. By the " Haftzotten "
the spongy mass is attached to the decidual surface. The
attached ends may excavate the decidua to some extent, but
there is no great degree of penetration (Fig. 128).
1 Kastschenko, " Das menschliche Chorionepithel und dessen Rolle bei
der Histogenese des Placenta," Arch.f. Anat. u. Phys., anat. Abth., 1885.
476 THE PHYSIOLOGY OF REPRODUCTION
As pregnancy advances, marked degenerative changes occur
in the maternal and foetal parts of the placenta. The most
notable change in the villi is the gradual disappearance of the
cytoblast, the mother-zone of the syncytium. Even the
" Zellsaulen " tend to disappear from the tips of the villi, and
their connective tissue comes in contact with the decidua.
Fibrinous changes are frequent in the remnants of the cytoblast
ca. sy. I). dec. ca. sy.
FIG. 128. — Diagram of stage in the development of the human placenta
(T. H. Bryce in Quairis Anatomy^ Longmans). The " Haftzotten " are
attached to the surface of the decidua. The mesodermic processes are
everywhere covered by a single layer of cells (Langhans' layer) and a
lamella of syncytium.
6., attachment of a villus ; mes., mesoderm ; ves.t vessels going to villi;
sy., syncytium ; L.I., Langhans' layer ; a., cross-section of a villus ;
dec., decidua ; ca., maternal capillary.
and in the mesoblast. The syncytium becomes very thin, and
occasionally tracts of it are stripped off.
The decidua serotina, after reaching its full development
during the third month, is gradually thinned out. This may be
partly due to the stretching of the tissue by the increasing growth
of the uterine contents, but it would seem also to depend on
conditions of malnutrition caused by the blood-stasis (Bonnet),
and the choking of the lymphatics by the decidual development
(Webster). The resulting degeneration takes the form of a
FCETAL NUTRITION: THE PLACENTA 477
coagulation necrosis or symplasma, as shown by the " Fibrin-
streifen," which are comparable to the fibrinous deposits in the
rabbit's placenta. The layers of fibrin in the serotina were first
described by Nitabuch.1 They may be seen as early as the
sixth wee'k, and even earlier in the reflexa (Webster). They
gradually extend more deeply into the substance of the decidua,
and also occur in the vessel walls. They are, however, most
marked on the surface, at or near the junction of the maternal
and foetal tissues. That they are due to the influence of the
ovum is highly probable from their absence in the vera. Whether
the symplasma is formed from the blood or the decidua, or both,
is not known. It is probably absorbed by the villous ectoderm
during the greater part of pregnancy.
According to Webster, there may be a new formation of de-
cidual tissue during pregnancy, from irregularly distributed
groups of active cells which are present at all periods in the
maternal part of the placenta (see p. 368).
The uterine glands take no part in the formation of the
placenta. By the sixth week their superficial parts are largely
obliterated, and the deeper parts degenerated. At a later stage,
only a few blind ends are seen next the muscular layer. Though
their epithelium offers a considerable degree of resistance, and
is visible for a long time, its secretory power is probably lost very
early. According to Gottschalk,2 the glandular epithelium
undergoes a fatty degeneration, but Bonnet3 states that the
change is a hyaline one. In the vera the glands increase in size
and secrete actively for a time. Their secretion is found as a
milky fluid in the uterine cavity.
Glycogen. — Glycogen is present in the early stages of preg-
nancy. Langhans 4 demonstrated it in the decidual cells, in the
cellular proliferations of the trophoblast at the tips of the villi,
and in the mesoblast. It was absent in the canalised fibrin and
1 Nitabuch, " Beitrage zur Kenntnis der menschlichen Placenta," Inaug.-
Dissert., Bonn, 1887.
2 Gottschalk, " Weitere Studien iiber die Entwickluug der menschlichen
Placenta," Arch. f. GynciJc., vol. xl., 1891.
3 Bonnet, " Ueber Syncytien," &c., Monatsschr. /. Geburtsh. u. Gynak.,
vol. xviii., 1903.
4 Langhans, " Ueber Glykogen in pathologischen Neubildungen und den
menschlichen Eihiiuten," Virchow's Arch., vol. cxx., 1890.
478 THE PHYSIOLOGY OF REPRODUCTION
Langhans' layer. Merttens 1 also found it in the decidua near
the ovum. Driessen 2 states that it is present in the superficial
and glandular epithelium of the uterus in the first month of
pregnancy ; around the ovum " in cells of doubtful origin/'
glycogen is plentiful, but absent in the deeper parts of the de-
cidua ; in the villi it is not found in the syncytium and Langhans'
layer, but is present in the cell-islands at the tips of the villi,
and occasionally in the mesoblast. The total amount is, how-
ever, much smaller than in Rodents, and represents only about
0'08 per cent, by weight (Cramer 3).
Fat. — Fat was first described in the human placenta by
Apfelstedt and AschofL4 They found it during the second
month of pregnancy in the syncytium and Langhans' layer,
and in the decidual cells near the villi. Eden 5 found fat in the
perinuclear protoplasm of the syncytium, and in Langhans'
layer and the stroma of the villi. It is also present in the
capillary walls (Dastre 6). The appearances suggested to Eden
that " the placenta appears to be a storehouse of nutritive fat
just as is the liver." Minute discrete droplets were also present
in the decidual cells, and by the sixth month they had increased
in number. At full time the serotina still contained fat, but
"it is doubtful whether now it is a physiological deposit, as the
serotina shows many degenerative changes." At the same time,
a fatty degeneration of the decidua is probably pathological and
not a constant phenomenon (Klein 7), and the fat globules in the
early stages represent an infiltration of fat into the decidual
cells from the maternal blood.
From the absence of fat in the more superficial parts of the
1 Merttens, "Beitrage zur normalen und pathologischen Anatomic der
menschlichen Placenta," Zeit. f, Oeb. u. Gynak., vols. xxx. and xxxi., 1894-5.
2 Driessen, " Ueber Glykogen in der Placenta," Arch. f. Gynak.,
vol. Ixxxii., 1907.
3 Cramer (A.), " Beitrage zur Kenntnis des Glykogens," Zeitschr. f. Biol.
vol. xxiv.
4 Apfelstedt and Aschoff, " Ueber bosartige Tumoren der Chorionzotten,"
Arch. f. Gynak., 1896.
5 Eden, " The Occurrence of Nutritive Fat in the Human Placenta," Proc.
Roy. Soc., London, vol. lx., 1896.
6 See Richet's Dictionnaire de Physiologie, vol. vi., Article "Fretus."
7 Klein, " Entwicklung und Riickbilduug der Decidua," Zeitschr. f.
Geburtsh. u. Gynak., vol. xxii.
FCETAL NUTRITION: THE PLACENTA 479
syncytium, Hofbauer 1 suggests that it may be split up into
fatty acids and glycerine before absorption, and then re-synthesised
by the foetal placenta (Fig. 129). Thence it is carried by the
blood in a soluble form, and is again deposited in droplets Jn
the heart, liver, lungs, alimentary tract, and spleen of the foetus.
In the later months of pregnancy there is a considerable deposit
of fat in the subcutaneous tissue.
•Ss
FIG. 129. — Fat in a villus of the human placenta. (From Hofbauer's
Biologic der menschlichen Plazenta, Braumuller.)
fs., fat globules in deeper layers of syncytium ; fs'., fat in syncytium between
Langhans' cells ; /&., fat in mesoblast ; fv.> fat in vacuolated cell.
Iron. — In Man, Peters found evidence of the presence of
red blood corpuscles in the trophoblast of the early ovum, and
Ulesco-Stroganowa 2 states that they are also present in the
syncytium in later stages. This has been disputed by
Kworostansky 3 and Hofbauer, who maintain that the corpuscles
are first dissolved. More recently Bryce and Teacher found no
evidence of the ingestion cf red blood corpuscles by the tropho-
blast, while Bonnet4 has shown that the syncytium gives the eosin-
1 Hofbauer, Orundzilge einer Biologic der menschlichen Plazenta, Leipzig,
1905.
2 Ulesco-Stroganowa, " Beitrage zur Lehre vom mikroskopischen Bau der
Placenta," Monatsschr. f. Geburtsh. u. Qyndk., vol. iii.
3 Kworostansky, " Ueber Anatomic und Pathologic der Placenta," Arch,
f. Oyndk., vol. \xx.
4 Bonnet, quoted by Hofbauer, loc. cit.
480 THE PHYSIOLOGY OF REPRODUCTION
reaction of haemoglobin at the points where it comes in contact
with extravasated blood. It has been stated that placental
extracts produce haemolysis in vitro (Veit and Scholten 1), but
whether a similar action takes place in the body is unknown.
Iron-containing compounds are also found in the villi.
Using the method of Hall, which
demonstrates iron in loose organic
compounds, Hofbauer found none such
in the superficial layers of the syncytium,
«~~iijSKVW hut an increasing number of granules
were present in the deeper parts. In
the mesoblast they again decreased in
number, and were altogether absent
near the capillary walls (Fig. 130). He
suggests that at first the haemoglobin
derivatives are in too firm combination
to take on the stain, then they are
further broken down and stained
granules appear, and later they are
again synthesised into non-stainable
compounds which reach the foetal
circulation. Such changes were char-
acteristic of the first half of pregnancy.
In the second half the iron-reaction of
the villi was " extraordinarily slight."
Iron is stored in the liver and other
foetal organs. According to Bunge,2 it
diminishes rapidly after birth, and he
supposes that it compensates for the insufficient amount of
iron contained in the mammary secretion.
Albumen. — The transmission of albumen to the foetus of the
rabbit has already been referred to (see p. 435). In the human
placenta attention has been chiefly directed to the investigation
of the decomposition products of proteins. Matthes 3 and
FIG. 130.— Iron granules
in a villus of the pla-
centa in Man. (From
Hofbauer's Biologic
der menschlichen Pla-
zenta, Braum tiller.)
1 Veit and Scholten, "Synzytiolyse und Hamolyse," Zeitschr. f. Geburtsh.
u. Oyndk., vol. xlix., 1903.
2 Bunge, "Ueber die Aufnahme des Eisens in den Organismus des
Sauglings," Zeit. /. phys. Chem., vol. xvii., 1893.
3 Matthes, "Ueber Autolyse der Placenta," Centralbl. f. Oyndk., 1901.
FCETAL NUTRITION: THE PLACENTA 481
Hofbauer state that albumoses are present in the placenta, but
this is doubtful. In watery extracts Rielander x demonstrated
purine bases, uracil and choline, and in the autolvsed placenta
leucine and tyrosine have been found (Basso 2). It is generally
held that such results prove an active metabolism of protein iiT
the foetal placenta.
Ferments. — Various enzymes have been investigated in the
placenta. They may be grouped according to the chemical
nature of the actions which they produce : —
Hydrolytic Reactions. — A proteolytic enzyme was found by
Ascoli,3 and subsequently by Merletti,4 Bergell and Liepmann,5
Savare,6 and others. Bottazzi 7 states that placental tissue can
transform glycogen into maltose, and a similar action is strongly
produced by glycerine extracts of the maternal and foetal
placenta of the rabbit (see p. 434).
Savare holds that the transformation of glycogen to sugar
is due to the blood ; but the fact that extracts of the ungulate
placentae, which also contain blood, do not possess the same
power, forces us to conclude that the enzyme activity in the
rabbit and Man depends on the placental tissue. No lipolytic
enzyme is present in the placenta (Charrin and Groupil 8).
Oxidation Reactions. — The oxidation of aromatic aldehydes
by the placenta has been obtained by Hofbauer and by Ferroni,9
not by Savare or Charrin and Goupil. V. Fiirth and Schneider10
state that tyrosine is oxidised by contact with the placenta,
1 Rielander, " Ein Beitrag zurChemie der Placenta," Centralbl. f. Gyndk.,
1907.
2 Basso, " Ueber Autolyse der Placenta," Arch. f. Gyndk., vol. Ixxvi.
3 Ascoli, " Passiert Eiweiss die placentare Scheidewand ? " Zeitschr. f.
phys. Chemie, vol. xxxvi. , 1902.
4 Merletti, " Ricerche e studi intorno ai poteri selettivi del' epitelio dei
villi coriali," Rass. d'Ost. e. Ginec., 1903.
5 Bergell and Liepmann, "Ueber die in der Placenta enthaltenen
Fermente," Munch, med. Woch., 1905.
6 Savare, " Zur Kenntnis der Fermente der Placenta," Hofmeister's Beitrdge,
vol. ix., 1907.
7 Bottazzi, " Placental Activity/' Boll, delta R. Accad. med. Genova,
vol. xviii.
8 Charrin et Goupil, "Physiologic du Placenta," Comp. Rend, de PAcad.
des Sciences ; vol. cxli., 1905 ; also vol. cxlii., 1906.
9 Ferroni, "L'eterolisi utero-placentare," Ann. di Ost. e Ginec., 1905.
10 V. Fiirth and Schneider, " Ueber tierische Tyrosinasen und ihre Bezie-
hungen zur Pigmentbildung," Hofmeister's Beitrdge, vol. i.
2H
482 THE PHYSIOLOGY OF REPRODUCTION
resulting in the production of a dark pigment, and they have
suggested that this reaction may be related to the special pig-
mentation of pregnancy.
Removal of amino-groups from amino-acids. — Savare states
that the placenta transforms the NH2 group of amino-acids into
ammonia by means of a special ferment, a desamidase.
Decomposition of peroxides. — This reaction may be produced
by enzymes, the so-called indirect oxidases, and is sometimes
regarded as the means by which oxidation changes are re-
stricted to the appropriate parts of the body, and secluded, for
instance, from the blood (Leathes *). The guaiacol reaction, by
which a colourless solution of guaiacol becomes red, takes place,
according to Charrin and Goupil, when hydrogen peroxide is
present ; in other words, placental tissue decomposes the
peroxide, and the nascent oxygen oxidises guaiacol. Hofbauer,
however, says that the presence of hydrogen peroxide is not
required, i.e. that the placenta acts as a direct oxidase.
Decomposition of glucose. — No glycolytic ferment is present
in the placenta.2
A few ferment actions still remain — e.g. the removal of urea
from arginin, the decomposition of uric acid, and the oxidation
of purine bases — which have not yet been investigated in the
placenta.
V. GENERAL CONSIDERATIONS OF FCETAL NUTRITION AND
THE PLACENTA
A. The Plan of Placental Formation
The problems of fcetal nutrition are not new problems. They
deal with the assimilation of organic and inorganic substances,
and their incorporation in the developing tissues. These
phenomena are made up of a series of chemical changes which
must be studied individually before we can hope to understand
the final sum which constitutes foetal metabolism, or the dis-
turbances which constitute foetal disease. Set in the path
1 Leathes, Problems in Animal Metabolism, London, 1907.
2 It cannot yet be held as proved that glycolysis by ferment action occurs
at all in animals.
FCETAL NUTRITION: THE PLACENTA 483
traversed by the materials on their way to the new organism is
the placenta, a complex organ composed of specialised maternal
elements and newly developed foetal elements. Among the
Monodelphia no uniform plan is observable in the formation of^
the placenta, nor is it possible to trace each step in its evolution.
But DuvaFs conception of this temporary organ as a maternal
haemorrhage surrounded by foetal elements, and Hubrecht's
discovery of such a type of placenta in a mammalian order
which is among the most archaic, lead to a change in the ideas
of placental classification. We can no longer depend on the
shape of the placenta, or the characteristics of the after-birth,
for an understanding of its morphological or physiological
features. Rather must we go back to the phenomena to be
observed in the uterine fixation of the blastocyst, and even
earlier in the preparation for that fixation. At this stage we
find two constant features, one maternal and the other foetal.
The maternal change consists of an epithelial, connective tissue
or endothelial proliferation, the trophospongia, which is
" specially intended for the fixation of the blastocyst." Ac-
cording to Hubrecht, it degenerates into a symplasma when the
fixation is accomplished and the foetal elements are in contact
with circulating maternal blood. But its degeneration is not
completed at that stage. Though individual cells may die,
other cells are formed and take their place, at least in Man,
throughout the greater part of pregnancy. Moreover, the cells
have other functions to perform. Whether or not they act as
a defence against the excessive penetration of the trophoblast,
they continue in the rabbit to exercise the glycogenic function
for the developing organism till the hepatic cells have attained
the power, and there is reason to believe that they play a part
in the iron metabolism of the foetus.
The embryonic preparation is the proliferation of the whole
or part of the extra-embryonic ectoderm, the trophoblast, in
the spaces of which maternal blood circulates. The outer layer
is plasmodial, and thus resembles the maternal symplasma in
histological appearance, but differs from it in being a live tissue
while the other is dying or dead. The fusion of the trophoblast
and trophospongia constitutes the placenta, which is perfected
by an increase in the number and size of the trophoblastic
484 THE PHYSIOLOGY OF REPRODUCTION
lacunae, and in the amount of maternal blood in contact
with it.
The above description does not, however, fit the placenta of
Ungulates, for in them the trophoblast is not permeated by
maternal blood. If the Insectivore placenta represents the
primitive type, or is nearer to it than any other at present
existing, we must assume that the Ungulate placenta, differing
more widely from the original type, has lost this characteristic.
Further, the placenta of the pig must have undergone a greater
degree of modification than that of the sheep. In other words,
the old ideas of placental evolution, based on the researches of
Turner and others, must be literally reversed. The Primates
must stand with the Insectivores near the primitive type, while
the sheep and pig are near the opposite end, where some of
the Didelphia are placed. Such considerations as these must
inevitably come up for discussion in all future investigations.
B. The Nature of the Trophoblastic Activity
During the period of gestation, the mother organism is
concerned with the provision of material for the growth and
development of the fertilised ovum and the new-born young.
Does the material provided for the ovum, and secured for it by
the trophoblast, come from the maternal tissues or from the
food supply ? There is no doubt that in insufficient nutrition
the foetus draws on the tissues of the mother (Jagerroos "*), and a
study of comparative placentation goes far to prove that this is
a normal process in some orders. It is obvious that such occurs
in the earliest stages. In all orders, before fixation of the
blastocyst to the uterine mucosa, the degenerating ovarian cells
which surround the extruded ovum form a store of nutriment.
In some animals, however, such as the opossum, in which no
attachment of the blastocyst can be said to occur, and the sheep,
in which the attachment is long delayed, this nutriment is
added to by the secretion of the uterine glands. In the so-
called Deciduate orders, fixation is effected by a phagocytic
or chemical action on the part of the trophoblast, and the
1 Jagerroos, " Der Eiweiss-, Phosphor-, und Salzumsatz wahrend der
Graviditat," Arch./. Gyr.dk., vol. Ixvii.
FCETAL NUTRITION: THE PLACENTA 485
destroyed maternal tissue again seems to serve as food for the
blastocyst.
After fixation, differences appear in the various orders. In
Ruminants a special nutritive secretion, the uterine milkj is_
elaborated in the inter-cotyledonary areas. This secretion con-
tains cellular elements of maternal tissue, particularly leucocytes
and glandular epithelium, which are ingested and dissolved by
the trophoblast during the whole period of gestation. In
addition, extravasations of maternal blood or individual cor-
puscles occur in all, and the erythrocytes are also taken up and
dissolved. In such orders maternal tissue elements are normally
used for the foetus throughout pregnancy.
Among the Deciduata, however, with the exception of the
mole, in which the glandular secretion is maintained, the
maternal blood may be considered to be the only source of
foetal nutriment when the allantoic or chorionic placenta is
developed.1 In them the trophoblast resembles a sponge
saturated with slowly circulating blood, and its large superficies
is admirably adapted for the acquisition of the various materials
required for the foetus. In what form do these materials exist
in the blood ? Are they simply the substances absorbed from
the food by way of the intestine (see also Chap. XI., p. 495), or
are they more highly elaborated ? In other words, in the
formation of the new organism are the syntheses carried out by
the fertilised ovum itself, and it must be remembered that this
includes the trophoblast, or are the new tissue-elements trans-
ferred ready-made from the mother ? The limitations of
biological chemistry force us to approach this problem indirectly.
Differential analyses of special constituents of the blood, as the
proteins, in the non-pregnant and pregnant animal are not yet
possible.
In the first place, a brief consideration of the development
of the chick embryo is sufficient to prove the high degree of
activity vested in the ovum of birds. The special proteins
and other tissue-elements are not pre-formed, but are elaborated
by a series of katabolic and anabolic processes which are carried
1 The Carnivora, in which the trophoblast is not in contact with circu-
lating maternal blood, occupy a special position among the Deciduata, and
are not considered above.
486 THE PHYSIOLOGY OF REPRODUCTION
out by the ovum itself. There is no reason to believe that the
mammalian ovum, after acquiring the property of intra-uterine
development, has lost its metabolic activity.1
In addition, we possess positive evidence of metabolic
activity in the mammalian ovum. The results of Bohr's in-
vestigations on the respiratory exchange of the foetus (see p. 436)
mean nothing if they do not afford proof of this. As a large
amount of energy is generated, while, at the same time, practically
none is dissipated as heat evaporated or radiated from the surface
or lungs, the unavoidable conclusion is that the foetus itself
carries out the work of organisation, and utilises the energy for
its fulfilment.
When we come to consider individual substances, we obtain
further evidence of activity, at least in the extra-embryonic
ectoderm or trophoblast. In no order of Mammals has the
transmission of haemoglobin as such from mother to foetus been
demonstrated. Even if it is absorbed as such by the tropho-
blast, it undergoes changes of such a nature that the iron-
containing part of the molecule is less firmly bound. In all
animals in which special investigations have been made, such
loose organic compounds of iron have been observed. In this
connection, reference may once more be made to Hofbauer's
statement that the histological appearances argue not only
for a decomposition of maternal haemoglobin in the syncytium,
but also for a synthesis of its derivatives into organic compounds
in which the iron is more firmly bound (see p. 480).
The trophoblast probably acts also on simpler proteins.
If ox- serum is injected into a pregnant rabbit, its proteins
cannot be detected by the biological reaction in the serum of
the foetus. It may be that the trophoblast rejects them
altogether, but this is unlikely, since molecules of egg-albumen
are absorbed and transferred to the foetus (see p. 436). In all
probability the proteins of ox-serum are katabolised in the villi,
and, as a result, the constitution of the precipitable substance
is interfered with, and the precipitin reaction is negative. The
1 If Hubrecht's view is correct, that the mammalian ovum is older than
the ovum of birds (see "Early Ontogenetic Phenomena in Mammals," Quar.
Jour. Micr. Sci., 1908), the sentence ought to read: "There is no reason to
believe that the fertilised ovum of birds acquired its metabolic activities only
after the loss of viviparity."
FCETAL NUTRITION: THE PLACENTA 487
existence of an intra-cellular proteolytic enzyme 1 and de-
composition products of the proteins in the placenta also
point to the occurrence of a trophoblastic metabolism of
proteins.
The carbohydrates undergo changes which appear to TTe"
the result of trophoblastic activity. In the rabbit, the glycogen
which is " swallowed " along with the decidual cells by the
plasmodium (Chipman) is not found as glycogen. A hydrolytic
transformation to sugar probably takes place (see p. 434). In
addition the foetal serum contains laavulose, which must be
formed in some part of the fertilised ovum, since it is absent in
the mother. Fats may also be transformed by the trophoblast
(see Chap. XL, p. 512).
It is generally supposed that many syntheses occur in the
fertilised ovum, though direct evidence is difficult to obtain in
Mammals. In the chick haemoglobin is synthesised, and the same
almost certainly occurs in Man and other animals, part of the
synthesis being effected by the trophoblast (see p. 480). The
nucleoproteins of the foetal cotyledons in the sheep appear to
be formed there, since they differ in composition from the nucleo-
proteins of the cotyledonary burrs. The glycoprotein mucin
is a characteristic constituent of the inter-cellular ground-
substance of the whole foetal organism, and is apparently built
up by the ovum.2 The chondroproteins, a special group of
glycoproteins, which yield on hydrolysis proteins and the
carbohydrate-containing chondroi tin-sulphuric acid, are also
found chiefly in the foetus as constituents of the cartilage and
tendons.
A consideration of these and similar facts leads us to believe
that the new organism owes its development in large part to
1 The enzyme has been found only in the human placenta. It is desirable
that its presence in the trophoblast should be established, and this can only
be done in such animals as the sheep and rabbit, in which the foetal placenta
can be detached from the maternal, and investigated separately. As was
previously mentioned, the placenta contains no extra-cellular proteolytic
enzyme.
2 In the placenta of the cow, Jenkinson has described cells resembling
goblet-cells in the lining of the cotyledonary crypts, and ascribes to them a
maternal origin (Proc. Zool. Soc., London, vol. i., 1906). They may supply
mucin to the uterine milk, and so to the trophoblast. According to Assheton,
these lining cells are trophoblastic in the sheep.
488 THE PHYSIOLOGY OF REPRODUCTION
the energy generated in it and by it from the combustion of
substances supplied by the mother, and to a series of active
metabolic changes by means of which these substances are
transformed into living protoplasm. Whether the nutritive
materials are derived from the food or tissues of the mother is
of secondary importance. What is essential is that the fertilised
ovum obtains certain organic and inorganic compounds and a
supply of oxygen to carry out its work of organisation, just as
in the first period of extra-uterine life the growth and develop-
ment of the new being progress by its own activities, so long
as it is furnished with the proper materials.
The special organ of embryonic nutrition is the trophoblast,
and evidences of its katabolic activities have been described in
various orders of Mammals. But in addition to procuring
fixation of the blastocyst to the uterine mucosa, and absorbing
and katabolising the food for itself and the embryonic portion
of the ovum, it seems also to possess anabolic functions, at
least in the earlier periods of pregnancy. Already developed
in the blastocyst stage, it is active and functional for a con-
siderable time. But in the later stages, it exhibits in all orders
of Mammals a degree of morphological degeneration which is
incompatible with the maintenance of its early physiological
activity. It is further to be noted that its condition varies
inversely with the food requirements of the embryo. When the
daily requirements for the new organism are almost infinitesimal,
the trophoblast is well developed. But as the daily transmission
of nutriment increases, the trophoblast, which is now repre-
sented by the ectodermal covering of the villi, gradually and
progressively degenerates. At the end of pregnancy the cyto-
blast, the mother zone of the plasmodiblast, is reduced to a few
scattered groups of cells, while the plasmodial layer itself is no
thicker than an endothelium, and may be altogether absent
over long stretches of the villi. At this stage it is impossible to
believe that the syncytium has any vital functions to perform.
Indeed, we know that it has none, because the foetus, if pre-
maturely born, is able to maintain life without its aid. Hence
it seems likely that in the later stages the extra-embryonic
ectoderm, though allowing a greater amount of material to
pass to the foetus each day, acts merely as a semi-permeable
FCETAL NUTRITION: THE PLACENTA 489
membrane, and has lost all, or nearly all, its physiological
activity.1
What is the difference in the early stages of pregnancy, when
the trophoblast is morphologically well -developed ? We believe
that at that time the extra -embryonic ectoderm has less to do
with the quantity, and more with the quality, of the material
transferred to the new organism. It does not act merely by the
physical laws of diffusion and osmosis. At this stage the cells of
the ovum have not yet departed widely from a general type, and
the active trophoblast would seem to spare the embryonic cells
much of the work of the elaboration of the food-materials, and
thus conserve their energies for their own multiplication and
differentiation. As the cells gradually depart further and in
different directions from the original type, each cell requires
to expend less energy on its own specialisation ; at the same
time the nutritive wants become more varied, and each cell
requires to expend more energy on the synthesis of its individual
protoplasm. As the duties of selection and anabolism are
more and more taken up by the cells themselves, the trophoblast
has a less important part to play, and it undergoes a gradual
process of degeneration.2
1 Hofbauer's observations on the haemoglobin metabolism, already quoted
(see p. 480), furnish concrete evidence of such a change in the trophoblast.
In the first half of pregnancy the syncytiutn breaks down the maternal
haemoglobin, and subsequently builds it up in part for the foetus. But in the
second half, though a greater daily supply of organic iron is required for the
formation of haemoglobin and other purposes (see p. 515), the amount of loosely
bound iron-compounds in the villi is " extraordinarily small." The only
explanation is that the larger molecules of the more firmly combined iron-
compounds are not attacked and broken down so strongly by the syncytium,
but are passed on to the foetal circulation.
2 A similar change occurs in the decidual cells of the rabbit. In the first
periods of their existence, they synthesise and store a large quantity of
glycogen. In the last week, the cells of the foetal liver assume their glyco-
genic function, apparently absorbing the carbohydrate from the foetal blood
as it returns from the placenta, and the decidual cells degenerate with the
loss of their function.
CHAPTER XI
THE CHANGES IN THE MATERNAL ORGANISM DURING
PREGNANCY l
" We cannot reason with our cells, for they know so much more than we
do that they cannot understand us ; but though we cannot reason with
them, we can find out what they have been most accustomed to, and what
therefore they are most likely to expect ; we can see that they get this, as
far as it is in our power to give it them, and may then generally leave the
rest to them." — SAMUEL BUTLER.
I. THE STIMULUS FOR THE MATERNAL CHANGES
THE anatomical and physiological changes which occur in
the maternal organism during pregnancy are manifold. They
affect not only the generative system, but the body in general.
They are associated with the supply of nutriment and energy
for the formation of a new organism in the uterus, and the
preparation for its maintenance in the succeeding period.
What constitutes the original stimulus for the changes that
occur in pregnancy remains still outside our ken. At least the
influence of the cerebrum is not all-important, as is shown by
the occurrence of normal pregnancy and lactation in women
suffering from paraplegia (Brachet,2 Kruieger and Offergeld 3).
Similarly, tran section of the spinal cord in the lumbar region
has no effect on pregnancy in the dog (Goltz 4). Further,
Goltz and Ewald 5 have proved the absence of any spinal reflex
influence in the dog by removing the entire lumbar cord
without disturbing the onset and progress of pregnancy.
Kruieger and Offergeld state, as the result of numerous experi-
ments, that the central nervous system has no influence, and the
1 By James Lochhead.
2 Brachet, Recherches, 2nd Edition, Paris, 1837.
3 Kruieger and Offergeld, "Der Vorgang von Zeugung, Schwanger-
schaft," &c., Arch.f. Gynak., vol. Ixxxiii., 1908.
4 Goltz, " Ueber den Einfluss des Nervensy stems auf die Vorgange wahrend
der Schwangerschaft," &c., Pfliiger's Arch., vol. ix., 1874.
5 Goltz and Ewald, "Der Hund mit verkurztem Riickenmark," Pfliiger's
Arch., vol. Ixiii., 1896.
490
CHANGES IN THE MATERNAL ORGANISM 491
sympathetic system has an effect only in so far as it modifies
the circulatory conditions. The only change observed, after
destruction of the lumbar cord, was a prolongation of the act
of parturition, due to an absence of pain and the consequent
loss of the reflex contractions of the abdominal muscles. The
most important nervous elements for the uterus are contained
in the uterine, paracervical, and para vaginal ganglia, but their
excitability for external stimuli gradually decreases during
pregnancy and is lost at the end.
We are thus forced to conclude that the phenomena of
pregnancy and parturition are brought about by chemical
stimuli acting through the blood-stream. The hormone or
hormones may arise in the corpus luteum, which is essential for
the progress of pregnancy, at least in the early stages (Marshall
and Jolly x). Evidence is also forthcoming that the mammary
secretion is due to an ovarian influence in certain cases. For
instance, secretion may occur in virgin women who are the
subjects of ovarian tumours, and in virgin bitches. Cramer 2 has
recorded a case in which the transplantation of ovaries into a
woman, whose genital organs were much atrophied, led to a secre-
tion of colostrum.3 On the other hand, removal of the ovaries
at the middle of pregnancy does not interfere with the second
half of the period of gestation, or with labour and lactation.1
The presence of the placenta may modify the normal meta-
bolism in various ways. It is set in the path traversed by the
formative material on its way to the embryo, and by the waste
products excreted by the embryo. The form in which the
materials required by the product of conception reach the
placenta is still obscure. The protein may be merely the
" circulating protein " found in the non-pregnant condition, or
more highly elaborated. The diffusion of the blood-sugar to
the foetus is disputable,4 and the form of the fats is unknown.
Of the waste products carbonic acid, which, according to Bohr,5
1 Marshall and Jolly, " The Ovary as an Organ of Internal Secretion,"
Phil. Trans.t Roy. Soc., London, B., vol. cxcviii., 1905.
2 Cramer (H.), "Transplantation menschlicher Ovarien," Munch, med.
Woch., 1906.
3 With regard to the existence of an ovarian stimulus, see also Hilde-
brandt (Hofmeister's Beitrage, vol. v., 1904). 4 See Chap. X., p. 434.
5 Bohr, " Der respiratorische Stoffwechsel des Saugetierembryo," Skand.
Arch. d. Phys., vol. x., 1900 ; also vol. xv., 1904.
492 THE PHYSIOLOGY OF REPRODUCTION
results entirely from the combustion of carbohydrates in the
mammalian foetus, is excreted into the maternal circulation
through the placenta. With regard to a wastage in the protein
metabolism, a certain loss is bound to occur in the transforma-
tion of " circulating " or " fixed " maternal proteins into foetal
tissue proteins ; and in addition, incompletely oxidised substances
may possibly be transmitted to the placenta and oxidised there
or in the mother (Bohr1). The question of urea formation by
the foetal liver or the trophoblast is still uninvestigated, and
no proof exists of the excretion of urea otherwise than into the
liquor amnii. Nor does its presence in the amniotic fluid
necessitate an oxidation of protein ; it may be split off, as in
the adult, by a simple hydrolytic cleavage. At present we must
be content with assuming the possibility of modifications in the
maternal blood from the presence of foetal nutritive and waste
materials. Hitherto the investigations have been largely con-
fined to human pregnancies, in which individual differences are
at a maximum, and the application ol the experimental
method is restricted. Hence our knowledge of the chemical
changes in the blood is very limited. Its composition may, in
addition, be modified by the activities of the placenta itself.
Several theories have been put forward in support of the view
that this organ acts as an internally secreting gland. Nattan-
Larrier 2 goes so far as to state that the secretion can be
demonstrated in the form of globules, lying on the surface of
the villi, but these arise in the post-mortem degeneration of
the tissue. Of the same nature are the products of the
placenta which have a blood-pressure raising action. Extracts
of the fresh organ have no pressor effects, nor do they increase
uterine contractions.3 Halban 4 considers that the placenta
secretes a hormone which stimulates the growth of the mam-
mary gland and the secretion of milk. Starling 5 states, on the
1 Bohr, see Nagel's Handbuch der Physiologic, " Respiration," vol. i., H.i.
2 Nattan-Larrier, "Fonction Secretaire du Placenta," Comp. Rend. Soc.
BioL, vol. lii., 1900. 3 See foot-note 2, p. 522,
4 Halban, " Die innere Secretion von Ovarium und Placenta, und ihre
Bedeuturig fur die Function der Milchdriise," Arch. f. Gyntik., vol. Ixxv.,
1905.
5 Starling, "Chemical Correlations of the Functions of the Body,"
Croonian Lect., Lancet, 1905.
CHANGES IN THE MATERNAL ORGANISM 4-93
other hand, that the hormone is contained in the tissues of the,
foetus.1 By its activity during pregnancy, it leads to a pro-
liferation of the mammary tissue, while the cessation of the
stimulus after parturition brings on the secretion of milk.
According to Liepmann,2 the maternal blood contains a
special protein, elaborated by the placenta, which may be re-
cognised by the biological reaction, and Freund 3 states that
the precipitable substance is present in the urine of pregnant
women. Others have been unable to find such a substance
either in the blood or urine (see Weichardt and Opitz 4).
Veit's 5 theory is also sub judice. Taking up SchmorFs 6
discovery that emboli of placental cells may be found in organs
of the mother in eclampsia, he extends it to normal pregnancy,
and postulates that syncytial fragments and even whole villi pass
regularly into the maternal circulation. There they give rise to
an an ti -body, a syncytiolysin, which itself dissolves the circulating
syncytium. He also seeks to explain, by the activity of the
lysin, the absorption of haemoglobin and other proteins from
the intervillous space by the villi, the pigmentation of the skin
and vaginal mucous membrane from superficial emboli, and the
phenomena of telegony from the circulation of elements derived
in part from the paternal side.7
1 It is conceivable that both views are right, since the main mass of the
placenta is as much a part of the fertilised ovum as the foetus itself. In
future investigations, the better recognition of the composite structure of
the placenta is desirable. In many animals it is possible to separate the
maternal and ftetal tissues with considerable accuracy, and any effect ob-
tained from one or other part can be definitely ascribed to the modified
uterine mucous membrane, or to the extra-embryonic part of the ovum.
2 Liepmann, " Ueber ein fur menschliche Plazenta spezifisches Serum,"
Deut. med. Woch., 1902, 1903.
3 Freund, " Beitrage zur Biologie der Schwangerschaft," Vortr. auf. d.
76 Naturf. zu Breslau, 1904.
4 Weichardt u. Opitz, "Zur Biochemie der Schwangerschaft," Deutsche
med. Woch., 1903.
5 Veit, " Ueber Deportation von Chorionzotten," Zeitschr.f. Geb. u. Gyncik.,
vol. xliv. Also Veit u. Scholten, " Synzytiolyse und Hamolyse," Zeitschr. f.
Geb. u. GyndJ>\, vol. xlix., 1903.
6 Schmorl, Path.-Anat. Untersuchungen uber die Puerperaleklampsia,
Leipzig, 1893.
7 The discussion of the relationship between the deportation of chorionic
villi and the pathology of eclampsia, pregnancy kidney, placental polypi,
hyperemesis, &c. , falls outside the scope of this work.
494 THE PHYSIOLOGY OF REPRODUCTION
At present it is only a speculation, as Veit himself is
careful to explain, but its far-reaching possibilities have already
given rise to many investigations.1 It must be clearly under-
stood, however, that biologists have at present no proof of
the formation of an anti-body consequent on the introduc-
tion of any protein of the same individual, or one of the same
species.
From time to time evidence of haemopoiesis in the placenta
has been brought forward. Mention of it was first made by
Masquelin and Swaen 2 in the rabbit, and later by Frommel 3 in
the mouse and bat. Hubrecht4 strongly upholds the occur-
rence of blood formation in the placentae of Tarsius and
Tupaia. The new erythrocytes arise as products of the frag-
mentation of nuclei of the trophoblast in Tarsius (see p. 410),
and of the trophoblast, and probably also trophospongia, in
Tupaia (see p. 457). They are later set free by solution of the
surrounding protoplasm. Such a process is beneficial both to
mother and embryo. The erythrocytes are increased at the
expense of the ovum, and they in turn increase the supply
of oxygen to the foetus.
II. CHANGES IN THE METABOLISM OF THE MOTHER
DURING PREGNANCY
A. The Source of the Materials transferred to the New
The question is discussed in another chapter (see p. 484)
whether the materials that go to the formation of the new
organism are entirely elaborated in the ovum itself, or are partly
1 See Kollmann, " Kreislauf der Plazenta, Chorionzotten und Telegonie,"
Zeitschr.f. BioL, vol. xlii., 1901.
2 Masquelin and Swaen, " Developpement du placenta maternel chez
le lapin," Bull, de I'Acad. Roy. de Belgique, 1879.
3 Frommel, Ueber die Entwicklung der Placenta von Myotus murinus,
Wiesbaden, 1888.
4 Placental haemopoiesis is denied by many authorities, including Duval,
Maximow, Nasius, and Nolf. For a complete review of the subject, see
Hubrecht, " Ueber die Entwicklung der Placenta von Tarsius und Tupoja,
nebst Bemerkungen iiber deren Bedeutung als hasmatopoietische Organe,"
Internal. Congr. of Zool., Cambridge, 1898.
CHANGES IN THE MATERNAL ORGANISM 495
or wholly prepared by the mother. As stated there, the histo-
logical and biological evidence leads us to believe that the
materials, whatever their source and constitution, are in the
early stages broken down and partly re-synthesised by the
trophoblast, while later in pregnancy they are metabolised by
the foetal cells themselves. Granting this, we must further
suppose that the maternal duties do not extend to the formation
of foetal tissue-components, but are limited to the provision of
food and oxygen for the fertilised ovum, the removal of its
waste products, and the preparation of an organ of nutrition for
the new-born young. Each of these duties leads to changes
in metabolism, which may, in addition, be excited by special
stimuli produced during pregnancy (see p. 491).
In the provision of nutriment for the embryo, does the
mother deplete her own tissues, or is she content to transfer the
unorganised substances, which are absorbed from the food and
not yet fixed as vital constituents of the protoplasm ? Pro-
bably both. In insufficient nutrition the mother certainly gives
up organised tissue-products, and, even with a plentiful diet, a
period is usually observed during which the mother must draw
on her own tissues to account for the loss of nitrogen. On the
other hand, it is probable that unorganised substances are also
utilised by the trophoblast, since variations in diet are ap-
parently capable of producing changes in the foetus.1 It was
noted by the writer and Dr. W. Cramer 2 that abortion oc-
curred in three out of six pregnant rabbits fed on a diet rich in
carbohydrates during the whole period of gestation. A similar
observation is recorded by Cramer and Marshall.2 Wallace 3
states that cows fed on molasses prove to be uncertain breeders,
and Heape 4 that Lincoln sheep fed solely on turnips are
specially liable to abortion.
1 Tbiemich was, however, unable to discover any difference in the consti-
tution of the foetal fat, after feeding the mother on widely different fats
(see p. 512).
2 See Cramer and Marshall, " A Note on Abortion as a result of a Diet
rich in Carbohydrates," Journ. of Econ. Biol., vol. iii. , 1908.
3 Wallace, Farm Live Stock, 1907.
4 Heape ascribes the frequency of abortion to the fouling of the turnip-
roots by mud and excrement, a condition of things which results from over-
crowding. See Journ. Roy. Agric. Soc., 1899.
496 THE PHYSIOLOGY OF REPRODUCTION
According to Noel Paton,1 the size of the offspring of the
guinea-pig depends very directly upon the diet and nutrition of
the mother during pregnancy. " To the physiologist it demon-
strates the limitations in the extent to which the tissues of the
mother can be utilised for the construction of the embryo.
The nourishment of the maternal tissues seems to take pre-
cedence over the nutrition of the foetus. The mother appears
to pass on the surplus nourishment to the foetus. The better
the nourishment of the maternal tissues, the greater the growth
of the foetus." On the other hand, it has been proved in the
pregnant rabbit that, when the glycogen of the body is reduced
to traces by repeated injections of phloridzin, the placenta and
foetus still retain considerable amounts.2 In this instance the
needs of the foetus have taken precedence over, the storage of
a carbohydrate reserve for the mother. Like Paton, Prochow-
nick 3 states that the size of the offspring may be markedly
diminished by restricting the diet of the mother (human female) ;
but many exceptions to this rule are found, unless the restriction
of food has been severe enough to jeopardise the life of the
mother.
This opens up another question : Does the expenditure for
the embryo entail loss to the mother ? "If the mother must
transfer a part, of her own bodily substance to the germ, the loss
is of little importance if she can cover this loss from her food.
The setting of the question runs thus : Is the maternal body
deprived of protein, fat, and other substances during and in
consequence of the formation of a new being, and is its store of
these materials, after the resulting birth, or at the close of the
puerperium, less than before the advent of pregnancy, or is this
not the case ? An unprejudiced clinical proof from human
subjects points to the possible occurrence of both conditions.
Many mothers during pregnancy increase so slightly in weight
that their own tissues must have suffered loss during this time,
others become heavier to the extent of ten kilograms or more.
1 Noel Paton, " The Influence of Diet in Pregnancy on the Weight of the
Offspring," Lancet, 1903.
2 Lochhead and Cramer, "The Glycogenic Changes in the Placenta and
the Foetus of the Pregnant Rabbit," Proc. Roy. Soc., London, B., vol. Ixxx.,
1908.
3 Prochownick, Therap. Monatshefte, 1901, quoted by Paton (loc. cit.).
CHANGES IN THE MATERNAL ORGANISM 497
The investigation has not to determine whether the maternal
organism suffers loss or experiences gain, but to demonstrate
under which conditions of nourishment the one or the other
appears. It has to investigate whether and in what amount
the needs of the mother are increased, if her original condition
is to remain unaltered while new tissues are being formed "
(Magnus-Levy 1).
B. The Body-weight during Pregnancy
Systematic determinations of the body-weight give some
idea of the effect of pregnancy on the maternal organism as a
whole. Gassner 2 observed a progressive increase in weight,
greater than the increase in the weight of the foetus (about
1 kilo per month) and the generative organs (about 0-125 kilo
per month) together. This is due to the increase in the other
parts of the maternal organism as a " result of the inactivity
and good dietetic conditions during pregnancy, and the fre-
quency with which the tissue fluids, e.g. in the lower extremities,
are increased/' Baumm 3 confirmed these results. A diet
necessary to maintain the body-weight in a woman of the same
size gave an increase in weight of a pregnant woman amounting
to an average of 1*777 kilo in the last month, of which
0'650 kilo represented increase outside the fcetus and generative
organs.
Zacharjewsky 4 observed an increase in weight running
parallel to the increased weight of the fcetus and uterus. Some
days before birth he found a decrease in primiparae and a balance
in multipart, which he referred to Ahlfeld's observations that the
foetus increases only up to the thirty-ninth week, and in the
last week decreases.
There are, however, limitations to the estimation of the
1 See v. Noorden, Metabolism and Practical Medicine, vol. i., section on
" Metabolism of Pregnancy."
2 Gassner, ' ' Ueber dieVeranderung des Korperge wichtes bei Sch wangeren,' '
&c., Monatsschr. f. Oeburtsh. u. Frauenkrankh., vol. xix., 1862.
3 Baumm, " Gewichtsveranderungen der Schwangeren," &c., Inaug.-
Dissert., Munch en, 1887.
* Zacharjewsky, " Ueber den Stickstoffwechsel wahrend der letzten Tage
der Schwangerschaft," &c.? Zeitschr.f. Biol., vol. xxx., 1894.
2i
498 THE PHYSIOLOGY OF REPRODUCTION
total metabolism by the alteration in weight. Thus Bar and
Daunay 1 discovered no increase of weight in a pregnant dog,
though it had retained 5*24 grammes nitrogen, equal to
170 grammes flesh. Such a discrepancy may be easily ex-
plained, for example, by a loss of water. In Man the physio-
logical variation in the water-content is as much as 2 kilo.
Hence it is necessary to obtain a more accurate measure, and
for this purpose to investigate separately the metabolism of
various substances, proteins, carbohydrates, fats, minerals, salts,
and oxygen. The available data are as yet too meagre to
demonstrate the good and the bad conditions of nutrition, but
they indicate the paths along which future investigations may
prove of value.
C. The Protein Metabolism in Pregnancy
a. The Absorption of Proteins by the Mother. — According
to Kehrer,2 the gastric functions are slightly below normal in the
human female during pregnancy. Free hydrochloric acid and
pepsin are each decreased by a third. At the same time the
intestinal functions appear to be sufficiently active for the
satisfactory absorption of nutriment.
The absorption of flesh does not show any characteristic
change in the dog during pregnancy. If decreased, it is due to
pathological conditions, and diarrhoea and vomiting are present
(Bar and Daunay). Ver Eeke 3 states that the absorption of
nitrogen decreases in the second half of pregnancy in the rabbit,
but he ascribes the change to mechanical conditions. Maurel 4
is of opinion that a gradual decrease in the nitrogen intake occurs
throughout pregnancy in the guinea-pig, but at the beginning
the intake is above the non-pregnant level. Zacharjewsky
found that only 4 to 6 per cent, of the nitrogen was un-
1 Bar and Daunay, " Bilan des ^changes azotes pendant la grossesse,"
Journ. de Phys. et de Path., vol. vii., 1905.
2 Kehrer, Die physiologischen und pathologischen Beziehungen der weib-
lichen Sexualorgane zum Tractus intestinalis, Berlin, 1905.
3 Ver Eeke, Lois des echanges nutritifs pendant la gestation, Bruxelles,
1901.
4 Maurel, " Des de'penses albuminoides pendant la grossesse chez le
cobaye," Comp. Rend. Soc. Biol., vol. Ixi., 1907.
CHANGES IN THE MATERNAL ORGANISM 499
absorbed by the human female in the last two weeks of
pregnancy, and Slemons l found 7 per cent, and 3 per cent,
in a primipara and a multipara respectively at the same
period.
b. The Daily Requirement of Protein for the Foetus. — The only
measure we possess of the extra protein required in pregnancy
is the amount deposited in the foetus and adnexa, the growing
uterus, and mammae. But this gives too low a figure, since one
gramme of tissue-protein requires more than one gramme of
food-protein for its manufacture. In addition, though we are
dealing with a period when anabolic processes are at a maximum
in the new organism, we are bound to assume that the cardiac,
hepatic, and other activities of the foetus, and the rhythmic con-
tractions of the uterus entail a certain loss of protein from wear
and tear. What these extra requirements amount to is un-
known, or whether protein substances play any part in the
provision of energy for the work of organisation.2
The amount of nitrogenous material deposited in the human
foetus during the last stages of pregnancy has been calculated.
Michel 3 estimates it at 56'69 grm. of nitrogen in two months, or
slightly under 1 grm. per day. Magnus-Levy 's figures are some-
what lower — 50 grm. in the last hundred days, or 0'5 grm. per
day. This represents only 3 grm. of protein, and when added
to the daily deposition in the placenta, uterus, and mammae,
it still remains inconsiderable.
c. The Nitrogen Balance in Pregnancy* — According to the
earlier investigators, a special economy of protein exists during
pregnancy. As Repreff 5 puts it, anabolic processes are in-
1 Siemens, "Metabolism during Pregnancy, Labour, and Puerperium,"
Johns Hopkins Hosp. Rep., vol. xii., 1904.
2 In so far as the work of organisation is carried out by the mammalian
foetus and not by the mother, the energy is probably supplied by the com-
bustion of carbohydrates alone (see p. 518).
3 Michel, " Sur la composition chimique de 1'embryon et du foetus
humain, " Comp. Rend. Soc. Biol., vol. li. , 1899.
4 See also v. Noorden's Metabolism and Practical Medicine, vol. i.,
Sect. IV. D., English Translation, 1907.
5 Repreff, " De 1'influence de la gestation sur les ^changes materiels,"
Russ. Dissert., 1888. Quoted by Slemons, loc. cit.
500 THE PHYSIOLOGY OF REPRODUCTION
creased and katabolic processes decreased in pregnancy in dogs,
rabbits, and guinea-pigs.
Hagemann 's l investigations in the dog form the first ac-
curate observations of the nitrogen balance during the whole
course of pregnancy. He set himself to solve the question
whether the new organism was formed from the food, or at the
expense of the maternal tissues. From the first experiment he
concluded that, even on a diet rich in nitrogen, there was a loss
of protein to the mother at the end of pregnancy. While
33-583 grm. nitrogen were retained, the young contained at
birth 7-445 grm. This left a balance of 26128 grm. for the
extra needs of the mother, which, he says, was nearly all
required for the formation of the foetuses (calculated at
16-6 grm.) and placentae (8'7 grm.). The additional nitrogen
required for the growth of the uterus and mammae must have
been derived from the maternal tissues. Hence the pregnancy
resulted in a loss to the mother. Similarly in lactation
34 '056 grm. nitrogen were retained, and the calculated excretion
in the milk was 76 grm. — a loss of 41/944 grm. nitrogen.
It is doubtful if such a conclusion is warranted, but the
figures have been given in some detail to illustrate some of the
difficulties to be overcome in carrying out the investigation.
Many troubles have been experienced in trying to keep the
animals on a constant diet, and, in addition, the increasing size
of the uterus may prove a mechanical difficulty and impede
the intestinal activity (Ver Eeke 2). Hagemann failed to obtain
the shed placentae, which were eaten by the mother animal.
Hence the estimate of 8'7 grm. nitrogen lost by them during
pregnancy and labour is arbitrary, and is, according to Bar and
Daunay,3 much too high. On these and other grounds — there
is a period of thirteen days during the pregnancy for which
no data are given — the calculations for pregnancy considered
as a unit are open to objection.
1 Hagemann, " Ueber Eiweissumsatz wahrend der Schwangerschaft und
Laktation," Arch. f. Anat. u. Phys., phys. Abth., 1890; also Inaug. Diss.,
Erlangen, 1891.
2 Ver Eeke, Lois des echanges nutritifs pendant la gestation, Bruxelles,
1901.
3 Bar and Daunay, "Bilan des echanges azote's pendant la grossesse,"
Journ. de Phys. et de Path., vol. vii., 1905.
CHANGES IN THE MATERNAL ORGANISM 501
On one point the results are of value. Hagemann states
that the period of gestation may be divided into two parts.
In the first, which lasts in his experiment for the first month of
pregnancy, there is a continuous loss of nitrogen to the mother
each day. In the second, there is a storage of nitrogen which is
used in the growth of the product of conception.
In Ver Eeke's experiments, nineteen in all, in the rabbit,
two phases were also frequently observed, but the results
varied widely. In some there was a positive balance throughout,
and in others a negative balance now at one time and now at
another. In the greater number the same diet was administered
before and after pregnancy and during its whole course. The
amount of protein did not far exceed the minimal requirement
for the maintenance of nitrogenous equilibrium.
Similarly variable results were obtained by Jagerroos l in
the dog.2 In his Experiment II. , in which the nitrogen content
of the food was high and the diet was pure flesh, there was a
positive balance each week except the second, 27*9 grm. nitrogen
in all being retained during pregnancy. In Experiment III.,
also on a diet of flesh but containing only 5'97 grm. nitrogen
per day, a negative balance occurred only in the fifth and sixth
weeks ; but when the weight of the foetuses and adnexa, and a
serious loss of nitrogen soon after labour were deducted, there
was a final loss to the mother of more than G grm. of protein.
In the last experiment the diet consisted of 60 grm. of
flesh and 100 grm. of sugar, which was just sufficient to
maintain nitrogenous equilibrium.3 It was maintained for the
first few days of pregnancy, and then a loss of nitrogen
occurred each week throughout the whole course of gestation
except the third.
In summing up the result of the three investigations, we must
still leave it undecided whether an increased katabolism of pro-
tein is characteristic of pregnancy as a whole, or is entirely de-
pendent on the diet. Hagemann's dictum that gestation entails
a sacrifice of protein on the part of the maternal organism is
1 Jagerroos, " Der Eiweiss-, Phosphor-, und Salzumsatz wahrend der Gravi-
ditat," Arch. f. Gynak., vol. Ixvii., 1903.
2 Jagerroos and Ver Eeke failed to secure the shed placentae.
3 Calculated over two days only.
502 THE PHYSIOLOGY OF REPRODUCTION
still unproven. Such is undoubtedly the case on a minimal
protein diet ; but, with a greater allowance of nitrogen, the con-
clusions of Hagemann and the others are not borne out by the
more recent researches of Bar and Daunay. They fed three
pregnant bitches on a constant diet of bread, water, fat, beef,
and salt, and estimated the nitrogen of the urine and faeces at
regular intervals. They took precautions to secure- the young
and the after-births, and were able to determine accurately
their nitrogenous content. In the three animals, as in two
observed by Jagerroos, the period of gestation was triphasic.
There were first a period of retention of nitrogen, then a balance
or very slight loss, and finally a retention increasing with the
progress of gestation. Further, there was over all a gain of
nitrogen in two dogs at the conclusion of labour. Hence they
conclude that pregnancy in a healthy animal, with a rational
and sufficient diet, does not necessitate a drain on her stock of
nitrogen to satisfy the needs of the foetus.
Jagerroos showed that, on a minimal protein diet, the
nitrogenous equilibrium was disturbed by the onset of pregnancy.
The loss of nitrogen began during the first week after conception,
when the fertilised ova were still in the oviduct or had just
reached the uterine cavity. At this stage the daily fixation of
nitrogenous substances in the young blastocyst is too small
in amount to affect per se the nitrogenous equilibrium. At the
same time there is an appreciable daily loss of nitrogen which
must be derived from the maternal tissues. It is permissible to
assume a relationship between the two facts, and argue that
the presence of the young blastocyst leads in some way to an
increased katabolism of protein.1 The daily loss of tissue is
maintained for a longer or shorter period during pregnancy,
according as the nitrogenous content of the diet is near the
minimum or more abundant. But, even on a comparatively
rich protein diet, it is generally accepted by the investigators
that a negative balance occurs for a considerable period, that
it then disappears, and is replaced by a positive balance lasting
1 It must, however, be kept in mind that the corpus luteum is undergoing
active changes at this period. As already stated, it is not known whether
the ovum or the corpus luteum provides the stimulus for the changes
referred to, or whether both of these are concerned (see p. 504).
CHANGES IN THE MATERNAL ORGANISM 503
till the end of pregnancy.1 In other words, during the period
in which the needs of the embryo are small the amount of
protein katabolised is not counterbalanced by the food protein,
and the maternal tissues suffer loss ; in the later period, although
the daily amount of nitrogen fixed by the new organism is con-~
siderably greater, the excreted nitrogen is more than counter-
balanced by the food nitrogen, and the maternal tissues gain,
or at least do not lose to such an extent as formerly. In the
human female, in whom investigations have been conducted
only in the last few weeks of pregnancy, a retention of nitrogen
has been invariably found. According to Zacharjewsky,2 it
amounted to a gain of 0*873 grm. per diem in primiparse and
5-05 grm. in multipart. On a diet usually containing less than
20 grm. nitrogen per day, Bar and Daunay observed an average
retention of 6 -54 grm. in three primiparae for eleven days in
the last month of pregnancy, a figure far exceeding that ob-
tained in the same women on the same diet a considerable
time after pregnancy.3
What is the reason for the increased katabolism of nitrogenous
substances during the earlier stages of pregnancy ? Hagemann
says : "In the transformation of maternal proteins into the
proteins of the growing uterus, embryos, and mammary glands,
some of the nitrogen-containing complexes of the molecules
lose their specific character, cannot be built up in the new protein
molecule, and are excreted in the urine." Ver Eeke suggests
that the loss of maternal blood may hasten protein katabolism,
and its reconstitution entail a sacrifice of nitrogenous substances
on the part of the mother. But it is not enough to say that the
loss of nitrogen is due to the inability of the cells to build up
protein synthetically, since no loss occurs on a sufficient diet
in the later stages of pregnancy, although the synthesis of new
tissue then reaches a maximum. Ver Eeke also states that the
greater katabolism in proportion to weight in growing than in
1 Kecently corroborated in the dog by Murlin ("Protein Metabolism in
Development," Amer. Journ. of Phys., vol. xxiii., 1908-9).
2 Zacharjewsky, " Ueber den Stickstoffwechsel wahrend der letzten
Tage der Schwangerschaft," Zeitschr. /. Biol., vol. xxx., 1894.
3 During the puerperium, the low diet administered to women entails
a loss of nitrogen to the maternal organism. Very variable times have
been noted in different cases before nitrogenous equilibrium was restored.
504 THE PHYSIOLOGY OF REPRODUCTION
grown animals may result in a negative nitrogen balance. But
in every other instance growth is associated, not with a loss,
but with a retention of nitrogen. The conditions are too com-
plex to admit of such a simple explanation.
With the onset of pregnancy certain parts of a grown organism
—uterus, mammae, &c. — are suddenly stimulated to growth.
At the same time a new organism is to undergo development.
Concurrently with these phenomena of grow '. h, a negative nitrogen
balance occurs in the first half of pregnancy ; that is to say,
pregnancy produces a change in the protein metabolism. In
the second half of pregnancy, growth is associated with a re-
tention of nitrogen by the mother. In other words, the con-
ditions which come into existence at the b ginning of gestation,
and lead to a negative nitrogen balance, alter during its course.
That growth proceeds along with a loss of nitrogen is note-
worthy. It is at variance with the conditions found in all
other instances of physiological growth, with which, however,
the growth of certain organs in pregnancy cannot be compared,
since it alone occurs in a grown mammal. It is conceivable
that this phenomenon in itself is sufficient to disturb the protein
metabolism. As was previously mentioned, it is not known
whether the stimulus for the changes during pregnancy is derived
from the fertilised ovum itself, the corpus luteum, or some other
less obvious factor. It has been experimentally proved that
the corpus luteum is essential in the early, but not in the later
stages.1 Its development dates from the period of conception,
and its activity lasts until the middle of pregnancy, after which
it undergoes structural and functional degeneration. Hence
the period of its activity corresponds with the period of the
negative nitrogen balance in the mother. Hagemann's observa-
tion of a similar nitrogen balance at a certain phase of the
oestrous cycle when corpora lutea are also developed, though no
ovum is fertilised, would seem to favour the view that the loss
of nitrogen is in some way connected with the changes in the
ovary.
Like the corpus luteum, the trophoblast undergoes a marked
change during pregnancy. In the early stages it forms the
special organ of nutrition for the embryo, and in addition to
1 Marshall and Jolly, loc. cit. (see pp. 336-345, 351, and 491).
CHANGES IN THE MATERNAL ORGANISM 505
absorbing nutriment it probably elaborates it into a form suit-
able for its incorporation in the new tissues. It is to this activity
that we may have to lo k f?r an explanation of the negative
nitrogen balance at the beginning of pregnancy. In the later
stages the ectoderm al covering of the villi loses its vitality,"
and seems to act more as a semi-permeable membrane (see p. 488).
The cells of the new organism are now more fully differentiated,
and are capable of carrying on their own metabolic functions.
d. The Nitrogen Excretion during Pregnancy. — The total
nitrogen excreted during the later stages of pregnancy is decreased
in amount. It again rises distinctly in the puerperium (Boni,1
Slemons 2). The urea nitrogen was stated to be normal in
amount by v. Winckel 3 and Zacharjewsky, but more recent
observations prove that it is diminished in proportion to the
total nitrogen. According to Matthews,4 it may fall below 13
grm. per day without any signs of insufficiency.5 The ammonia
nitrogen, which is of interest in connection with the question
of acidosis in pregnancy, is relatively increased, but at present
no proof is forthcoming that it is absolutely higher than in the
non-pregnant state. The relative increase is due to the decrease
in the total nitrogen (Slemons, Matthews). In eclampsia,
Zweifel 6 has frequently observed an increase of the ammonia
nitrogen to 10 per cent, or more of the total, and, associated
with it, the presence of an organic acid in the urine. The
acidosis, at least in a certain number of the cases, is the result of
the eclamptic seizures. Further investigations of the conditions
when no fits have occurred are necessary before any constant
association of an acidosis with the disease can be affirmed.
The uric acid excretion is within physiological limits. The
1 Boni, " I corpi purinici nelle urine delle gravide e delle puerpere,"
Ann. di Oat. e Gin., 1906.
2 Slemons, " Metabolism during Pregnancy," &c., Johns Hopkins Hosp.
Rep., vol. xii., 1904.
3 V. Winckel, Studien iiber den Sto/wechsel, &c., Kostock, 1865.
4 Matthews, "The Urine in Normal Pregnancy," Amer. Journ. Med. Sc.,
vol. cxxxi., 1906.
5 There are, however, wide physiological variations according to the
N-content of the diet.
6 Zweifel, "Die Eklampsie," Arch. f. Gyndk., vol. Ixxii., 1904.
506 THE PHYSIOLOGY OF REPRODUCTION
figures given by Zacharjewsky are 0*603 grm. per day in primi-
parse, and 0*531 grm. in multipart. Boni states that it is almost
normal in amount, but his figures are considerably lower than
the average given by Magnus-Levy for a mixed diet.1 Boni
observed a diminution in the purine bases which varied between
4-7 and 6-8 per cent.2
V. Leersum 3 states that in 40 per cent, of pregnant women
on the usual hospital diet, the amino-acid nitrogen amounts to
over 10 per cent, of the total nitrogen, whereas it varies between
2 *7 and 7*7 per cent, in the non-pregnant. The maximum
is usually reached before birth, and there is a decrease later.
Sometimes the maximum does not occur till after birth, but
the acids may then be derived from the involution of the uterus.
The results, according to this investigator, argue for a dis-
turbance of the liver even in apparently normal pregnancies,
its power of splitting off ammonia from and oxidising the amino-
acids being impaired.4
The albuminuria of pregnancy in the human female is not
strictly physiological. Regarding its frequency very varying
figures have been given, ranging from 5 per cent, to 60 per cent.
It appears in the second half of pregnancy, gradually increases
up to the time of birth, and quickly decreases in the puerperium.
In 50 per cent, of the cases it has already disappeared on the
fourth day after labour. The protein is of renal origin, and in
a typical case amounts to 0*01 to 0-05 per cent. That it is not
due to mechanical pressure on the renal vessels or ureter, or to
increased intra-abdominal pressure, seems certain. Nor has any
definite proof been given of the influence of a toxin arising in the
foetus', and causing degeneration of the renal epithelium. Veit 5
1 As uric acid is derived in part from the nucleins of the food, no
conclusions can be drawn from its estimation on an unknown diet.
2 The average value is 8 per cent, on a mixed diet.
3 V. Leersum, " Die Ausscheidung von Aminosauren wahrend der Schwa.ng-
erschaft," Biochem. Zeitschr., 1908 ; Fest. f. Hamburger.
4 It has not yet been proved that the liver is the only organ which
possesses this function. The placenta itself is stated to contain a desamidase
(Savare, " Zur Kenntnis der Fermente der Placenta," Hofmeister's Beitr.,
vol. ix., 1907 ; see also p. 482), hence the increase in amino-acid nitrogen
may be due to a disturbance of placental function.
5 Veit, " Ueber Albuminurie in der Schwangerschaft," Berlin, klin.
Woch., 1902.
CHANGES IN THE MATERNAL ORGANISM 507
explains it by his hypothesis of the presence of placental con-
stituents in the maternal circulation. Metabolic investigations
in pregnancy complicated by albuminuria show nothing charac-
teristic (Magnus-Levy 1).
A special constituent of the urine may be found during The~
puerperium. Though called peptone (Fischel2), it really con-
sists of deutero-albumoses which arise from the involution,
i.e. autolysis, of the uterus (Langstein and Neubauer 3). As with
similar proteins introduced subcutaneously, the organism has
not the power of splitting them up, and they are excreted un-
changed. Fischel stated that peptonuria might also occur in
pregnancy ; but this was disproved by Thomson,4 who also
showed that a puerperal peptonuria did not regularly exist.
Ehrstrom 5 regards it as a certain indication of fever and sepsis,
the peptone being contained in the leucocytes of the purulent
lochia.
As a result of the involution of the uterus, creatin may also
appear in the urine. Murlin 6 kept a dog on a creatin-free diet
during the last week of pregnancy. The creatinin output was
constant, but creatin appeared two days before parturition.
It reached a maximum five days after labour — the period when
the involution processes reach their height.
D. The Carbohydrate Metabolism in Pregnancy
a. The Absorption of Carbohydrates by the Mother. — The
starch digestion is said to be retarded in the stomach during
pregnancy (Kehrer 7). Little is known regarding the absorp-
tion of carbohydrates, but there is evidence of a tendency to
1 Magnus-Levy, see v. Noorden, loc. cit.
2 Fischel, " Peptongehalt der Lochien,"Arch.f. Gyndk., vols.xxiv. andxxvi.
3 Langstein and Neubauer, " Autolyse des puerperalen Uterus," Munch,
med. Woch., 1902.
4 Thomson (H.), " Ueber Peptonurie in der Schwangerschaft und im
Wochenbett," Deutsche med. Woch., 1889.
5 Ehrstrom, "Puerperale Peptonurie," Arch. f. Gyndk., vol. Ixiii., 1901.
6 Murlin, "Protein Metabolism in Development," Amer. Journ. of Phys.,
vol. xxiii., 1908-9.
7 Kehrer, Die physiologischen und pathologischen Beziehungen der
Weiblichen Sexualorgane zum Tractus Intestinalis, Berlin, 1905.
508 THE PHYSIOLOGY OF REPRODUCTION
abortion in certain animals on a diet containing them in excess
(see p. 495).
b. Carbohydrates of the Maternal Organism. — Lactose may
appear in the blood in pregnancy as well as during the lactation
period. Lsevulose is not present in the serum of a healthy
animal ; but it is normally present in the allantoic fluid of the
cow (Giirber and Griinbaum x), and in the blood-serum of the
foetal rabbit, cow, and sheep (Paton 2). Whether it is the only
monosaccharide present has not yet been determined, but it is in
sufficient amount to render the serum laevo-rotatory.
The glycogen store of the liver is stated to be increased in
pregnancy in the dog (Burlando 3), in the guinea-pig (Maurel 4),
and in the human female (Charrin and Guillemont 5). There is
no increase in the rabbit. The placenta contains glycogen in
varying amounts. It is found only in traces in Ruminants, but
in great amount in Rodents (see Chap. X., p. 431). It occurs also
at the margin of the zonary placenta in Carnivores, and in the
human placenta. In many species it has not yet been investi-
gated.
In the foetus, the feature of the glycogen is not its high
percentage, but its almost universal distribution in the de-
veloping tissues.6 It has been shown by Bohr that the energy
in the mammalian foetus is supplied by the combustion of
carbohydrates (see p. 518), and by the wide distribution of
1 Giirber and Griinbaum, " Ueber das Vorkommen von Lavulose im
Fruchtwasser," Munch, med. Woch., 1904.
2 Paton, Watson (B. P.), and Kerr, "On the Source of the Amniotic and
Allantoic Fluids in Mammals," Trans. Roy. Soc. Edin., vol. xlvi., 1907.
The proof that the carbohydrate is lasvulose rests on the laevo-rotation of
the plane of polarised light and the ketone reaction. Doubts have recently
been expressed regarding the sufficiency of these two tests.
3 Burlando, " Behaviour of Hepatic Glycogen during Menstruation,
Pregnancy, Puerperium, and Lactation Period," Arch. Ital. di Oinec., 1906.
4 Maurel, " Des defenses albuminoides pendant la grossesse chez le
cobaye," Comp. Rend. Soc. Biol., vol. Ixi., 1907.
5 Charrin and Guillemont, "Physiologic pathologique de la Grossesse,"
Comp. Rend. Soc. de Biol., 1899.
6 Gierke, "Glycogen in der Morphologic des Zellstoffwechsels," Habili-
tationsschrift, Freiburg, 1905. See also Lochhead and Cramer ("The
Glycogenic Changes in the Placenta and the Foetus of the Pregnant Babbit,"
Proc. Roy. Soc., London, Ser. B., vol. Ixxx., 1908), from whose memoir the
Table is copied.
CHANGES IN THE MATERNAL ORGANISM 509
glycogen an available supply is procured in every part of the
foetal body in which the work of organisation is proceeding.
c. The Daily Requirement of Carbohydrate for the Fostus. —
Some idea can be obtained of the daily requirements of glycogen_
for the foetus of the rabbit in the second half of pregnancy.
The appended table gives the amount of glycogen contained in
the unborn young from the eighteenth day of gestation till the
day before parturition : —
Day of
Gestation.
Average Weight
of each Foetus
in Grammes.
Average Amount
of Glycogen
per Foetus.
Number of
Foetuses.
Total Amount of
Glycogen.
18
0-89
•0018
8
•0144
20
2-32
•0050
6
•0300
21
3-28
•0080
5
•0400
22
4-13
•0103
4
•0412
23
7-20
•0203
8
•1624
24
9-75
•0346
6
•2076
25
20-23
•0808
7
•5656
26
11-24
•0257
5
•1285
27
32-84
•1418
3
•4254
28
32-07
•2017
6
1-2102
29
26-67
•1199
9
1-0791
TABLE to show the foetal weight and amount of foetal glycogen
in the second half of pregnancy (rabbit). In the animal killed at
the twenty-sixth day, the pregnancy was abnormal, one foetus being
dead and the others badly developed. In the last also the foetuses
were unusually small.
The table shows that 1*2 grm. of glycogen are deposited
between the eighteenth and the twenty-eighth day, or about 0-2
grm. per foetus. Hence the average daily deposition is O02 grm.
per foetus. In the later stages the rate of deposition increases
out of proportion. This is due to the assumption of its glycogenic
function by the foetal liver.
The amount of carbohydrate oxidised each day can be
calculated from Bohr's figures. The oxygen consumption for a
foetus weighing 30 grm. is 0*14 c.cm. per minute. This is sufficient
to oxidise 0-00017 grm. of sugar, or 0'245 grm. per day, which is
equal to 0*227 grm. of glycogen. Hence for six foetuses, the
average number, 1*362 grm. are required for combustion each
day. In addition, an average of 0'3 grm. of glycogen is deposited
510 THE PHYSIOLOGY OF REPRODUCTION
in them daily near the end of pregnancy. Hence the total daily
requirement for the unborn young at this stage is 1'662 grm. of
glycogen. A small additional amount of carbohydrate is re-
quired for the daily increasing blood-serum, for the liquor
amnii in the rabbit, and for the manufacture of mucin and
other glycoproteins.
d. Excretion of Carbohydrates in Pregnancy : Glycosuria and
Lactosuria. Blot * was the first to postulate the occurrence
of a " physiological glycosuria " in pregnancy. Kirsten 2
found sugar in the urine in the majority of cases of pregnancy
and labour, and regularly in the puerperium. Hofmeister 3
first discussed the relationship of the glycosuria to milk secre-
tion, and proved that the sugar excreted in the puerperium
was lactose.4 The sugar is in extremely small amounts, but
above the normal. Lemaire 5 found 0-003 to 0-009 per cent.,
and Brocard 6 an upper limit of 0-01 per cent. Zacharjewsky,7
however, observed no increase in the reducing power of the
urine on an ordinary diet during the last weeks of pregnancy.
The first definite increase conies with the appearance of lactose
in the urine after birth, though it may also be excreted a few
days before birth. It is more evident when the milk is not
utilised and becomes re-absorbed, but it rarely exceeds 0*3 per
cent.8 Extirpation of the mammary glands immediately stops
the lactosuria,9 and, if carried out in pregnancy, prevents it.10
1 Blot, "De la glycosurie physiologique chez les femmes en couches,"
&c., Comp. Rend. Soc. Biol.t vol. xliii., 1856.
2 Kirsten, " Ucber das Vorkommen von Zucker im Harn der Schwangeren,"
Monatsschr. f. Geburtsh. u. Frauenkrankh., vol. ix., 1857.
3 Hofmeister, " Ueber Laktosurie," Zeitschr. f. phys. Chem., vol. i., 1877.
4 Corroborated by Kaltenbach (" Die Laktosurie der Wochnerinnen,"
Zeitschr. f. Geburtsh. u. Gyndk., vol. iv.) and many others.
5 Lemaire, " Ueber das Vorkommen von Milchzucker," Zeitschr. f. phys.
Chem., vol. xxi., 1895.
6 Brocard, " La Glycosurie de la Grossesse," These de Paris, 1898.
7 Zacharjewsky, loc. cit., Zeitschr. f. BioL, vol. xxx., 1894.
8 The inability of the organism to oxidise lactose was demonstrated by
Voit (" Verhalten der Zuckerarten im menschlichen Organismus," Deut. Arch,
f. klin. Med., vol. Iviii., 1897).
9 Sinety, " Urine of Guinea-Pigs in Puerperium," Comp. Rend. Soc. Biol.,
vol. 1.
10 V. Noorden, loc. cit., vol. i. (see also pp. 571-573).
CHANGES IN THE MATERNAL ORGANISM 511
The glycosuria of pregnancy has been ascribed to a diminished
glycolysis (Brocard), and to hepatic inadequacy (Cristalli J),
without sufficient evidence. The greater tendency to ali-
mentary glycosuria in pregnancy was upheld by Lanz.2 He
frequently observed it after the administration of 100 grm. of
glucose. On the other hand, Payer's 3 careful experiments
showed an assimilation limit of 130 grm. of glucose, which is not
subnormal, the excess being very rapidly excreted. Hence it
must be left unsettled whether a more ready saturation of the
maternal organism may be brought about in pregnancy, and
whether this is related to an increased storage of carbohydrate
at this time.
E. The Metabolism of Fats in Pregnancy
a. The Absorption of Fats by the Mother. — The absorption of
fats from the intestine is increased during pregnancy (Ferroni 4),
the neutral fats, fatty acids, cholesterin, and soaps contained
in the faeces being all decreased towards the end of the
gestation period. This is the time when the subcutaneous
tissues of the foetus receive an abundant supply. They rapidly
reach the normal level in the puerperium. There is a corre-
sponding increase of fat in the maternal blood in the dog and
guinea-pig, and the excess disappears after parturition (Capaldi 5).
b. Fat of the Maternal Organism. — According to Miotti,6 the
liver cells contain a continuously increasing amount of fat, first in
the central parts of the lobule and later throughout. He looks
on it as a fatty infiltration, and concludes that an increased fat
formation takes place during pregnancy.
1 Cristalli, Ricerche sulla presenza dello zuchero nelle orine delle donne
gravide e puerpere, Naples, 1900.
2 Lanz, " Ueber alimentare Glykosurie bei Graviden," Wien. med. Presse,
1895.
3 Payer, " Einfluss des Zuckers auf den Stoffwechsel der Schwangeren,"
Monatsschr. f. Geburtsh. u. Gyntik., vol. x
4 Ferroni, " I grassi neutri . . . delle gravide e delle puerpere sane,"
Ann. di Ost. e Ginec., 1905.
5 Capaldi, "Sul contenuto di grasso del sangue nella gravidanza e nel
puerperio," Ann. di Ost. e Ginec., 1905.
6 Miotti, "Contribute allo studio istologico de fegato durante la gravi-
danza," Ann. di Oat. e Ginec., 1900.
512 THE PHYSIOLOGY OF REPRODUCTION
In the placenta there is evidence of a transmission of fat to
the product of conception. Even in the early stages of preg-
nancy the cells of the uterine mucosa are infiltrated with fat,
and the trophoblast is pervaded with fat globules. In Ungu-
lates a large amount of fat is contained in the uterine milk
(see p. 403). In those mammalian orders, in which the tropho-
blast is directly bathed by maternal blood, the fat dissolved in
it forms a second available supply. There is no reason to doubt
an active transference of fat from the mother, or to assume that
a transformation from carbohydrates or proteins is necessary.
c. The Daily Requirement of Fat for the Foetus. — The daily
requirement of fat varies very considerably during pregnancy,
and especially towards the end, when the subcutaneous fat of
the foetus is deposited. Fehling 1 found 0'5 per cent, of fat
in the human foetus at the fourth month, over 4 per cent, at the
eighth, and 9 per cent, at the ninth month.
d. Origin of the Fatal Fat. — As to its origin, Thiemich 2 states
that it is not derived from the alimentary fat of the mother,
since after feeding a dog in two successive pregnancies on widely
different fats, palmin and linseed oil, he could determine no
difference in the constitution of the foetal fat. Oshima 3 comes
to the same conclusion from his investigations on the number
of ultra-microscopic particles in the blood of cats, rabbits, and
guinea-pigs. He states that the number is dependent on the
stage of development, and independent of the condition of the
mother's blood — for example, when a great increase is produced
by rich fat-feeding. Capaldi, on the other hand, states that the
percentage of fat is the same in the maternal and foetal blood,
at least at the end of pregnancy. Some feeding experiments
carried out by Hofbauer 4 agree with this. He administered
coco-nut oil 5 to three pregnant guinea-pigs, and demon-
1 Fehling, " Beitrage zur Physiologic des placentaren Stoffverkehrs,"
Arch.f. Gyncik., vol. xi., 1877.
2 Thiemich, " Ueber die Herkunft des fotalen Fettes, Centralhl. f. Phys.,
vfcl. xii., 1898.
3 Oshima, "Ueber das Vorkommen von ultra-mikroscopischen Teilchen
im fotalen Blute," Centralbl. f. Phys., vol. xxi., 1907.
4 Hofbauer, Biologie der menschlichen Plazenta, Wien and Leipzig, 1905.
5 It consists essentially of the triglycerides of laurinic and myristinic acids
with a very small quantity of tripalmitin.
CHANGES IN THE MATERNAL ORGANISM 513
strated laurinic acid in considerable amount in the foetuses.
Hence the fat of the food, or at least one of its fatty acids,
had been transmitted across the placenta. But any conclusions
based on the introduction of a foreign fat must be guarded.
In the foetus, fat is present in many of the tissues in a stale "
of fine division. Its wide-spread distribution and its amount,
probably equal at least to that of glycogen, are a characteristic
of foetal life ; but its significance is not obvious if, as Bohr
states, it is not a source of energy. Guillot l showed that it did
become a source of energy immediately after birth. He found
12 per cent, of fat in the lungs of foetuses dying during labour,
and only 6 per cent, after several hours* respiration. Fat may
have anabolic functions to perform in the building up of the
foetal body, e.g. in the synthesis of lecithin.
e. The Excretion of Fat Derivatives in Pregnancy. — The
primary product is oxybutyric acid. This, by oxidation, is
transformed to aceto-acetic acid, which in turn gives rise to
acetone by the loss of carbon dioxide from the molecule. Little
is known regarding the excretion of aceto-acetic acid and oxy-
butyric acid in apparently normal pregnancies, though in patho-
logical cases of persistent vomiting, with a high degree of inanition,
the latter may often appear (Kraus 2). This is to be expected.
In general, if the amount of oxybutyric acid is small, acetone
alone appears in the urine ; if in greater amount diacetic acid
may also be present, and, if greater still, all three maybe excreted.3
That acetonuria exists in pregnancy is certain, but in the
majority of cases it does not pass the physiological limit
(Stolz 4). If it is in greater abundance, some special factor must
be at work, It is not enough to say that its presence is always
due to the exclusion of carbohydrates in varying degrees from
the metabolism,5 leading to a lowered oxidation of fats by the
1 Guillot, quoted in Richet's Dictionnaire de Physiologic, Article " Foetus."
2 Kraus, quoted in v. Winckel's Handbuch der Oeburtshulfe, vol. i., H. 1.
3 See v. Noorden, loc. cit., vol. i.
4 Stolz, "Die Acetonurie in der Schwangerschaft," Arch. f. Gyndk.,
vol. Ixv.
5 Wolfe ("The Chemistry of Toxaemias in Pregnancy," New York Med.
Journ., 1906) states that there is no connection between acetone compounds
in the urine and the essential features of hyperemesis gravidarum', a condi-
tion in which there is pre-eminently a deficient absorption of carbohydrates.
2K
514 THE PHYSIOLOGY OF REPRODUCTION
cells of the body. When no change is made in the ordinary
diet, when no signs of dyspepsia are present and no glycosuria
exists, we are not justified in assuming a withdrawal of carbohy-
drates from the metabolism. Rather is it related to the aceton-
uria arising after chloroform and ether narcosis (Beesly) 1 or in
febrile conditions — that is, it is toxic in origin. It has, however,
still to be discovered whether the acetonuria of pregnancy is
associated, as the acetonuria of narcosis 2 and of fever (Regnard 3
and Geppert 4), with a diminished alkalinity of the blood.
F. The Metabolism of Metals and Salts in Pregnancy
Little is known regarding the metabolism of the individual
metals and salts. The fixation of mineral elements is slight
at the beginning, but becomes active towards the end of
pregnancy. From first to last, about a hundred grammes
are transferred from the mother to the human fcetus. With
a few exceptions, the mineral salts are approximately in the
same proportion throughout pregnancy. The exceptions are
sodium, potassium, and calcium, of which sodium decreases and
calcium increases with the replacement of cartilage by bone,
and potassium increases with the increased manufacture of
red blood corpuscles (Hugounenq 5).
a. Iron. — Part at least of the iron for the foetus is derived
from the haemoglobin of the maternal organism.6 In the
poly-cotyledonary placenta of Ruminants and the zonary placenta
of Carnivores, the disintegration of red blood corpuscles has
been demonstrated. There is less certainty regarding the actual
ingestion of the red cells by the syncytium of the discoid placenta,
1 Beesly, " Post-Ansesthetic Acetonuria," Brit. Med. Journ., 1906.
2 Beesly and Milne, unpublished paper.
3 Regnard, Combustions respiratoires, 1879.
4 Geppert, "Die Gase des arteriellen Blutes im Fiebcr," Zeitschr. /. Iclin.
Med., vol. ii.
5 Hugounenq, "Rechercb.es sur la statique des elements mineraux et
particulierement du fer chez le foetus humain," Comp. Rend. Soc. Biol.,
llth series, vol. i., 1889.
6 It is doubtful whether haemoglobin is an " organised " protein, hence
its disintegration does not, as might be supposed, afford proof of the trans-
mission of maternal tissue protein to the fcetus.
CHANGES IN THE MATERNAL ORGANISM 515
though it has been described by Peters in an early human ovum.1
But in all placentae yet investigated, iron-containing granules
have been observed in the trophoblast. The possible sources
are haemoglobin, which is in part absorbed as such by the tropko^
blast in Man (Bonnet 2), nucleoprotein, and the reserve iron of
the mother. Nuclein is the only iron-containing constituent of
yolk of egg, and must serve for the manufacture of haemoglobin
in the developing chick. It is also known that in the adult
organism nucleoprotein is a better source of iron for haemoglobin
than any inorganic or other organic compound hitherto ad-
ministered by the mouth.3 Hence it is not difficult to conceive
that the same process may occur in the foetus. But whether it
is the food nucleoproteins or the organised nuclein bodies of
the maternal organism that are utilised, is unknown.4 With
regard to the reserve iron of the mother, it is stated by Charrin 5
that the store in the spleen is reduced during pregnancy.
In the foetus iron is required for the synthesis of haemoglobin
(see p. 480) and nucleoproteins.6 Large amounts of iron are
also stored in the liver and other organs. According to Bunge's 7
law, this forms a reserve which is drawn on after birth to make
up for the deficiency of the iron in the milk. Thus the liver of
a rabbit contains 18 mg. of iron per 100 grm. body-weight at
birth, and only 3*2 mg. twenty-four days later.
According to Veit and Scholten,8 the villi can dissolve intact
red cells of the circulating blood, just as the solution of erythro-
1 See Chap. X., p. 479. 2 See Chap. X., p. 480.
3 V. Noorden, foe. cit., vol. i., p. 78.
4 As the purine bases of the urine are stated to be decreased in pregnancy
(see p. 50G), the maternal nuclein s are probably not a source of iron for the
foetus to any appreciable extent.
5 Charrin, " Physiologic pathologique de la grossesse," Comp. Rend. Soc.
de Biol., 1899.
6 The nucleoproteins of the foetal placenta in the sheep differ in their
chemical constitution from those of the maternal placenta. They are
probably synthesised in the ovum from lower complexes, in the same way
as the nucleoproteins of the chick embryo are built up though the egg
contains no purine bases.
7 Bunge, " Weitere Untersuchungen iiber die Aufnahme des Eisens in
den Organismus des Sauglings," Zeitschr. f. phys. Chem., vols. xvi. and
xvii., 1892-3.
8 Veit and Scholten, " Synzytiolyse and Haemolyse," Zeitschr. f. Qeburtsh.
u. Gynak., vol. xlix.
516 THE PHYSIOLOGY OF REPRODUCTION
cytes can be produced by placental extracts. As a result
of this, hsemoglobinsemia may occur in pregnancy. Wychgelg
observed it in eight out of twenty-three pregnancies, and the
condition occurs more frequently still in eclampsia. At present,
however, it is not yet generally accepted that an erythrotoxin is
formed by the syncytium, though Bonnet2 has shown histo-
logically that a destruction of red cells probably takes place
during life. He noticed on the surface of the villi " perfect and
damaged erythrocytes in all stages of degeneration, clumping
and solution/' So Hofbauer found, by adding neutral-red to
the chorionic villi of two fresh two-months' placentae teased in
saline, that many of the blood corpuscles showed red dots
indicating degeneration.
b. Calcium. — The source of the foetal calcium is still un-
settled. According to Drennan,3 it is derived from the circulat-
ing blood and not from the tissues of the mother, but he adduces
no strong evidence. It is well known that the teeth are apt to
become brittle in pregnancy from a decrease in calcium fluoride 4
and a deficiency in enamel formation. Evidence of a special
drain on calcium is also found in puerperal osteomalacia,
which occurs in poor people who presumably have an insufficient
supply of calcium in their diet.
c. Phosphates and Sulphates. — It has been generally found
that the phosphoric acid excretion runs parallel to the nitrogen
(V. Eeke,5 Schrader 6). Jagerroos,5 however, showed an equili-
brium between intake and output in a pregnant dog which
showed a distinct loss of nitrogen. According to Schrader,
the excretion of sulphates is parallel to that of nitrogen.
1 Wychgel, " Untersuchungen iiber das Pigment der Haut und der Urin
wahrend der Schwangerschaft," Zeits. f. Geburtsh. u. Gyndk., vol. xlvii.
2 Bonnet, quoted by Hofbauer (Biologie der menschlichen Plazenta, Wien
und Leipzig, 1905).
3 Drennan, "The Abstraction of Calcium Salts from the Mother's Blood
by the Foetus," New York Medic. Journ., vol. Ixxxvii.
4 Terrier, " De 1'Influence de la Grossesse sur les Dents," These de Paris,
1899.
5 V. Eeke, Jagerroos ; see pp. 500 and 501 for references.
6 Schrader, "Stoflfwechsel wahrend der Schwangerschaft," Arch. /.
Gyndk., vol. x., 1900.
CHANGES IN THE MATERNAL ORGANISM 517
d. Chlorides. — The first estimations of the chlorides of the
urine in pregnancy indicated no variation from the non-
pregnant level (Winckel 1). Repeated investigations have been
carried out since the discovery that a retention of chlorides
may occur in nephritis and lead to oedema (Widal 2).
Biancardi 3 stated that cedemas in pregnancy were sometimes
due to the same cause, and might be cured by decreasing the
chlorides of the food. Next Cramer 4 affirmed that all cases of
hydrops graviditatis without albuminuria were due to a re-
tention of sodium chloride ; and Boni, whose careful investiga-
tions of the urine in pregnancy have already been referred to,
found that the chlorine excretion was decreased, and remained
low during the puerperium. Along with this there is a retention
of water to maintain osmotic balance. Normally 90 to 100 per
cent, of the water taken in is excreted in the urine, but the
percentage fell to 72 per cent, in a primipara, 53 per cent, in a
multipara, and 48 per cent, in a twin pregnancy (Siemens 5). . Such
a retention did not occur in a woman who was later delivered of
dead twins, 93 per cent, of the water being excreted in the urine.
Birnbaum's 6 results are not in agreement with the others.
He states that a retention of chlorides occurs only in the
nephritis of pregnancy, and not in normal pregnancy or in
hydrops without albuminuria. In the blood-serum the
chlorides were 0*1740 per cent, and 0-1775 per cent, in two cases,
and 0-1733 per cent, in a non-pregnant woman.
G. Respiratory Exchange during Pregnancy
Modifications in the respiratory exchange arise from the
alterations in the maternal organism, and from the requirements
1 Winckel, Studien iiber Stoffwechsel, &c., Kostock, 1865.
2 Widal, " La cure de dechloruration dans le mal de Bright," Arch. Gener.,
vol. cxciii., 1904.
3 Biancardi, "Sulla cura declorurante nelle nefriti e nelle albuminurie
nel campo ostetrico," Ann. di Ost. e Ginec., 1905.
4 Cramer, " Chlornatrium-Entziehung bei Hydrops Graviditatis," Monats-
schriftf. Geburtsh. u. Gynak., vol. xxiii.
s Siemens, "Metabolism during Pregnancy, Labour, and Puerperium,"
Johns Hopkins Hosp. Rep., vol. xii., 1904.
6 Birnbaum, " Excretion of Chlorides during Pregnancy," Arch. f. Gyndk.,
vol. Ixxxiii., 1907.
518 THE PHYSIOLOGY OF REPRODUCTION
of the product of conception. To a certain extent diffusion of
oxygen takes place from mother to foetus, as it has been proved,
by experiments in asphyxia of the mother, that the direction
in which oxygen goes across the placenta depends on the tension.
Whether there is also a gas-secretion by the trophoblast is
unknown.
With regard to the foetus, Pfliiger argued on theoretical
grounds that the oxidation processes were inconsiderable, and
the oxygen intake small. This was confirmed experimentally
by Cohnstein and Zuntz.1 More recently, however, Bohr2
has shown by more convincing experiments that in the later
stages of pregnancy the foetal guinea-pig consumes at least as
much oxygen as the mother. The actual figures which he ob-
tained were 462 c.cm. for the mother and 509 c.cm. for the foetus
per kilo per hour. He has also shown that the foetal respiratory
quotient is unity, indicating that carbohydrates are the source
of energy. The same has been found in new-born puppies
before suckling (Murlin 3). It is well to remember that Bohr's
experiments refer only to the foetus in the later stages of de-
velopment, and that they entirely leave out of account the
placental metabolism.4
The high consumption of energy in the foetus, which differs
from the adult in losing little heat by radiation from the skin
surface and lungs, must be due to the intensive growth of the
embryo (see Chap. X., p. 434).
1 Cohnstein and Zuntz, " Untersuchungen iiber das Blut, den Kreislauf,
und die Atmung beim Saugetierf 6'tus, " Pfliiger's Arch., vol. xxxiv., 1884.
2 Bohr, " Der Respiratorische Stoffwechsel des Saugetierembryos," Skand.
Arch.f. Phys., vol. x., 1900.
3 Murlin, "Protein Metabolism in Development," Amer. Journ. of Phys.,
vol. xxiii., 1908-9.
4 In the later stages tbere is a wide distribution of glycogen throughout the
tissues of the foetus, and the foetal liver has assumed its glycogenic function.
It is scarcely justifiable to extend Bohr's results to the early stages of
pregnancy, when the placenta probably takes a leading part in embryonic
development. It may be that at that time also glycogen is the source of
energy for the placenta in Rodents, but it cannot be so in Ruminants. In
their placentae glycogen is found only in traces, while fat is in consider-
able amount. Hence we cannot assume that the energy is derived from
the combustion of carbohydrates until experimental evidence has been
obtained.
CHANGES IN THE MATERNAL ORGANISM 519
It is possible, though not yet proved, that, in addition to
carbonic acid, incompletely oxidised substances may be brought
to the placenta from the foetus and oxidised there or in the
mother (Bohr 1). Such a hypothesis lies at the foundation_of
the theory that certain pathological conditions in pregnancy
are due to the circulation of toxins manufactured in the product
of conception.
With regard to the total energy exchange, the results of
Magnus -Levy,2 F. Muller,3 and E. Zuntz 4 tend to show that in
the human pregnancy no decrease in metabolism occurs, the
metabolic changes being at least as active in the foetus as
in the mother. In one experiment Levy found a progressive
increase in the oxygen intake during pregnancy, but he does
not lay too much stress on the figures,5 as in all the others no
increase in the gaseous exchange per kilo was established.
Even in the third month there was a marked increase. The
weight increased from 108*4 to 111 '4 kilo, and the oxygen
intake from 302 to 320 c.cm. per minute, i.e. from 279 to
2'88 c.cm. per kilo per minute. With such figures we
must conclude that the early stages of pregnancy have had
a favourable influence on the growth of the mother
animal, and at the same time have led to a more energetic
metabolism.6
1 Bohr, Nagel's Handbuch der Physiologic, " Kespiration."
2 Magnus-Levy, " Stoffwechsel und Nahrungsbedarf in der Schwanger-
schaft," Vortrag, Zeitschr. f. Geburtsh. u. Gynak., vol. Hi. ; also v. Noorden,
loc. cit., vol. i.
3 F. Muller, " Diskussion zum Vortrag von Magnus-Levy," see v. Noorden,
loc. cit., vol. i.
4 E. Zuntz, " Der Stoffaustausch zwischen Mutter und Frucht," Ergebn. d.
Phys., 1908.
5 The older investigations of Oddi and Vicarelli ("Influence de la gros-
sesse sur 1'echange respiratoire," Arch. ital. de Biol., vol. xv., 1891), showed a
progressive increase in the consumption of oxygen during the last third of
pregnancy in rats ; but Magnus-Levy raises the objection that the movements
of the animals were not restricted.
6 Such a result is in conformity with those obtained in rats soon after
inoculation with malignant new growths ; Cramer (W.), " The Gaseous Meta-
bolism in Eats inoculated with Malignant New Growths," 3rd Scient. Rep.,
Imperial Cancer Research Fund, London, 1908). Magnus-Levy's exceptional
result may, however, be due to the fact that the woman under observation
had not yet completed her growth.
520 THE PHYSIOLOGY OF REPRODUCTION
III. THE CHANGES IN THE MATERNAL TISSUES DURING
PREGNANCY
The changes in the ovaries, the mammae, and the mucous
membrane of the uterus are dealt with elsewhere. To the
changes in some of the other organs, a brief consideration is
here given.
a. The Blood. — Ehrlich's 1 statement that pregnancy does
not appreciably alter the number of the red blood corpuscles
has been more or less firmly established by Ingerslev,2 Dubner,3
Bernhard 4 and others in Man, by Spiegelberg and Gscheidlen 5
in the dog, and by Cohnstein 6 in the sheep. Their investi-
gations have upset the older theory of a hydraemia of pregnancy.
There is evidence of a slight increase of haemoglobin (Payer,7
Fehling,8 Winckelmann,9 Wild 10), especially towards the end of
pregnancy.
The number of leucocytes increases during pregnancy, and
there is a further rise during the act of parturition (Nasse,11
Lebedeff,12 Rieder 13). The leucocytosis is referred by some to
1 Ehrlich, " Die Anamien," in Nothnagel's Spezielle Pathologic.
2 Ingerslev, " Ueber die Menge der roten Blutkorperchen bei Schwangeren,"
Centralbl.f. Gyndk., 1879.
3 Dubner, " Untersuchungen iiber den Hamoglobingehalt des Blutes," &c.,
Munch, med. Woch., 1890.
4 Bernhard, "Untersuchungen iiber Hamoglobingehalt und Blutkorper-
chenzahl in der letzten Zeit der Schwangerschaft," Munch, med. Woch.,
1892.
5 Spiegelberg and Gscheidlen, " Untersuchungen iiber die Blutmenge
trachtiger Hunde," Arch. f. Geburtsh. u. Gyndk., vol. iv.
6 Cohnstein, " Blutveranderungen wahrend der Schwangerschaft," Pfluger's
Arch., vol. xxxiv., 1884.
7 Payer, vide v. Winckel's Handbuch der Geburtshiilfe , vol. i., H. 1.
8 Fehling, "Ueber Blutbeschaffenheit," &c., Arch. /. Gyndk., vol. xxviii.,
1886.
9 Winckelmann, " Hamoglobin-Bestimmungen bei Schwangeren und
Wochnerinnen, Inaug. Diss., Heidelberg, 1888.
10 Wild, " Untersuchungen iiber den Hamoglobingehalt und die Anzahl
der roten und weissen Blutkorperchen bei Schwangeren," Arch. f. Gyndk.,
vol. liii.
11 Nasse, Das Blut, Bonn, 1836.
12 Lebedeff, quoted in v. Winckel's Handbuchder Geburtsh iilfe., vol. i., H. 1.
13 Rieder, Beitrdge zur Kenntnis der Leukocytose und verwandter Zu-
stande des Blutes, Leipzig, 1892.
CHANGES IN THE MATERNAL ORGANISM 521
the lymphoid tissue of the endometrium, and by others to an
increase in the groups of lymphatic glands in the neighbourhood
of the genital apparatus.
According to Spiegelberg and Gscheidlen, the total amount^
of blood is increased during pregnancy in the dog from 7 '8 per
cent, to 9 per cent, of the body-weight. There is no essential
difference in the specific gravity (Nasse, Blumreich l). The
observations on the alkalinity of the blood are few and con-
tradictory. Lebedeff states that it is increased, and similarly
Blumreich, who investigated the blood of pregnant rabbits
and women. The alkalinity quickly returned to the normal
level. On the other hand, Payer's estimations of the
" diffusible " alkali, i.e. alkali not combined with protein,
of defibrinated blood give values slightly below the non-
pregnant level. The molecular concentration of the blood
shows no change during pregnancy.
b. The Heart and Circulation. — Older authorities stated that
a true hypertrophy of the heart occurred during pregnancy,
and was caused by the increased length and size of the uterine
vessels, the placental circulation, and the compression of the
aorta by the gravid uterus. Experiments showed, however,
that the uterine vessels did not offer a resistance which required
an increase in the work of the heart (Engstrom 2), while the
compression of the abdominal aorta and the introduction of
large quantities of fluid into the abdominal cavity produced no
change which could be detected from the pulse (Heinricius 3).
The controversy has been a long one, but it does not properly
belong to this article. The present-day opinion of the cardiac
modifications in the human female may be summed up as
follows : Tendency to dilatation, especially of the right heart,
and to some compensatory hypertrophy. The frequent em-
barrassment of the right ventricle, even in the early stages of
pregnancy, is marked by the occurrence of shortness of breath
1 Blumreich, "Der Einfluss der Graviditat auf die Blutalkalescenz,"
Arch. f. Gyndk., vol. lix., 1899.
2 Engstrom, " L'Influence de la grossesse sur la circulation," Arch, de
Gyn., 1886, vol. ii.
3 Heinricius, Experimentelle und klinische Untersuchungen uber Circula-
tionsverhalten der Mutter und der Frucht, Helsingfors, 1889.
THE PHYSIOLOGY OF REPRODUCTION
and palpitation and by changes in the rate and rhythm of the
heart. An increased area of dullness to the right of the sternum
can usually be made out, but it is mainly due to the abnormally
transverse position of the heart, and to its greater contact with
the anterior wall of the chest (v. Winckel l).
It has been suggested that the increased work of the heart,
which leads in many cases to the dilatation of its chambers
and perhaps to some compensatory hypertrophy, is due to an
increased peripheral resistance from the presence of a vaso-
constricting substance in the blood.2 In excess it may cause
anuria and eclampsia (Nicholson 3).
The blood-pressure is not affected in normal pregnancy,
but is always raised in labour as a result of the uterine con-
tractions. After parturition the pressure falls, but rises again
on the third day of the puerperium.
Varices of the lower extremities and external genitals are
frequent in human pregnancy. They are due mainly to the
increased intra-abdominal pressure and the stretching of the
abdominal wall. Secondary thromboses are common in the
puerperium.
c. The Ductless Glands. — There is regularly a swelling of the
thyroid gland in pregnancy (Tait4), which consists of a simple
hypertrophy, and not a vascular engorgement or cystic change
(Freund 5). It has been shown experimentally in cats that a
1 V. Winckel, loc. cit., vol. i., H. 1. This has been clearly established
by radiograms of the thorax in pregnancy.
2 The origin of this substance, if such exists, is still unknown. The
investigation of extracts of the placenta by the writer, in conjunction with
Dr. W. Cramer, proved that this organ contained no blood-pressure raising
substance. The substances extracted by Dixon and Taylor ("On the Physio-
logical Action of the Placenta," Proc. Roy. Soc. of Med., London, vol. i.,
1908) from the placenta and observed to have an adrenalin-like action,
were subsequently shown to arise in the course of putrefaction (see Rosenheim,
Journ. ofPhys., 1909).
3 Nicholson, "The Maternal Heart in Pregnancy," Brit. Med. Journ.,
1904, part ii.
4 Tait, "Enlargement of the Thyroid Body in Pregnancy," Obstet. Journ.,
1875.
5 Freund, " Ueber die Beziehung der Schilddriise," &c., Deuts. Zeitschr.
f. Chir., vol. xxxi., 1890.
CHANGES IN THE MATERNAL ORGANISM 523
remnant of the gland, which is sufficient to maintain health in
the non-pregnant state, is insufficient after the onset of preg-
nancy (Lange *).
An increased suprarenal secretion in pregnancy has also been_
suggested, the effect of which on the blood pressure is normally
balanced by the increased thyroid secretion (Nicholson 2). But
experimental evidence seems to show that the blood-pressure
raising action of the suprarenals is entirely independent of the
thyroid gland (Pick and Pineles 3).
d. The Skin. — The cause of the increased pigmentation of
the skin in pregnancy is little understood. It has been looked
on as a simple deposit of pigment, as the result of infection with
the microsporon furfur, the cause of pityriasis versicolor which
not infrequently attacks pregnant women, and as a subcutaneous
haemorrhage.4 Jeannin 5 first suggested that it was derived
from haemoglobin set free by the solution of red blood corpuscles.
According to Veit 6 the haemolysis may be produced by the
circulation of syncytial elements in the blood. The presence of
iron in the pigment, though strongly denied by Truzzi,7 has
recently been demonstrated by Wychgel.8 He associates its
presence with the frequent occurrence of haemoglobinuria in
pregnancy. V. Fiirth and Schneider's suggestion that the
pigment is derived from tyrosin by the action of a placental
tyrosinase is mentioned elsewhere (Chap. X., p. 481).
An abnormal development of the hair of the face and body
1 Lange, "Die Beziehungen der Schilddriise zur Schwangerschaft,"
Zeitschr.f. Geburtsh. u. Gynak., vol. xl., 1899.
2 Nicholson, " Physiological Changes in the Maternal Organism during
Pregnancy," Trans. Obstet. Soc. Edinburgh, vol. xxxi., 1905-6.
3 Pick and Pineles, " Beziehung der Schilddriise zur physiol. Wirkung
des Adrenalins," Biochem. Zeitschr., vol. xii., 1908.
4 See v. Winckel's Handbuch der Geburtshiilfe, vol. i. H. 1.
5 Jeannin, "Observations pour servir k 1'histoire du masque des femmes
enceintes," Gaz. Hebdom., 1868.
6 Veit and Scholten, " Synzytiolyse und Hamolyse," Zeitschr. f. Geburtsh.
u. Gynak., vol. xlix., 1903.
7 Truzzi, " Ueber die Genese der Hyperchromie der Haut in der Gravi-
ditat," Monatsschr. f. Geburtsh., vol. xi., 1898.
8 Wychgel, " Untersuchungen iiber das Pigment der Haut und den Urin
wahrend der Schwangerschaft," Zeitschr. f. Geburtsh. u. Gyntik., vol. xlvii.
524 THE PHYSIOLOGY OF REPRODUCTION
is occasionally seen in pregnancy (Slocum,1 Halban 2). Under
the name of dermographismus, Freund 3 describes a phenomenon,
often met with in pregnancy, similar to the tache cerebrate of
meningitis and other nervous affections. It may be elicited
even in the early stages of gestation, and is best shown by
stroking the skin over the sternum or fundus uteri.
e. The Mammce. — The growth of the mammary glands is
brought about by the development of new vesicles, the widening
of existing blood-channels, and the formation of new vessels.4
Even in the first half of pregnancy, and sometimes in the first
weeks, the mammae contain colostrum, a milky fluid composed of
proteins, albumen, globulin, and casein, the carbohydrate lactose,
fat, free fatty acids, lecithin, cholesterin, free glycero-phosphoric
acid, and urea (Winterstein and Stickler 5).
1 Slocum, " Hair Development in Pregnancy," New York Med. Rec., 1875.
2 Halban, " Zur Frage der Graviditatshypertrichose," Wien.lclin. Woch.,
1907.
3 Freund, " Die Haut bei Schwangeren," Verhandl. d. vi. deutsch. Der-
matologen-Kongr. zu Strassburg.
4 See Chapter XIII.
5 Winterstein and Stickler, "Die chemische Zusammensetzung des
Colostrums," Zeitschr. f. phys. Chem., vol. xlvii., 1906.
CHAPTER XII
THE INNERVATION OF THE FEMALE GENERATIVE
ORGANS— UTERINE CONTRACTION— PARTURITION— THE
PUERPERAL STATE
" Birth is the end of that time when we really knew our business, and the
beginning of the days wherein we know not what we would do, or do." —
SAMUEL BUTLER.
THE innervation of the generative organs of the male was dealt
with at some length in an earlier part of this work. It remains
in the present chapter to describe the nerve supply to the female
generative system, and more particularly to the uterus, since this
is the organ which is especially concerned in the process of
parturition. But before giving an account of the innervation
of the internal organs, the nerve supply to the vulva and clitoris
may be briefly dealt with.
THE INNERVATION OF THE EXTERNAL GENERATIVE ORGANS
The external generative organs in the female are similarly
innervated to those of the male (p. 254 et seq.).
Langley and Anderson l found that stimulation of the first
five lumbar nerves in the cat, or the third, fourth, and fifth
lumbar nerves in the rabbit, produced the same effects as in
the male excepting that they were less pronounced. The effects
were (1) Pallor of the clitoris and of the mucous membrane of
the vulva, accompanied by slight retraction of the clitoris,
(2) Contraction of the vulva, and (3) Contraction of the muscles
of the adjoining skin, drawing the vulva dorsally towards the
rectum.
Langley,2 and subsequently Langley and Anderson,3 found
1 Langley and Anderson, " The Innervation of the Pelvic and Adjoining
Viscera," Jour, of Phys., vol. xix., 1895.
2 Langley, "The Innervation of the Pelvic Viscera," Proc. Phys. Soc.,
Jour, of Phys., vol. xii., 1891.
3 Langley and Anderson, loc. cit.
525
526 THE PHYSIOLOGY OF REPRODUCTION
that two groups of effects, which were antagonistic to one
another, could be produced by stimulating the sacral set of
nerves in the vertebral canal, but that, as in the male, only
those fibres which exercised an inhibitory influence run from
the spinal cord in the sacral nerve roots. The inhibitory effects
produced were (1) Flushing of the vulva and clitoris, (2) Dilata-
tion of the vulva, and (3) Relaxation of the skin muscles sur-
rounding the vulva. The visceral motor effects were the same
as those produced by the lumbar set of nerves as described
above. Besides these effects, contraction was induced in the
external sphincter of the vagina and in the striated genital
muscles.
THE INNERVATION OP THE OVARIES
The ovary is innervated from the sympathetic plexus ac-
companying the ovarian artery and from the plexus associated
with the ovarian branch of the uterine artery. It is generally
supposed that the nerve fibres, which are non-medullated, are
merely vascular in function.1 The fact that ovulation in some
animals only occurs as a consequence of coition, and then takes
place at a definite time afterwards, points to the conclusion
that the follicles discharge in response to a stimulus conveyed
to the ovary by its nerves (see p. 134). It has been suggested
that the rupture is due to the stimulation of erectile tissue.2
Nerve fibres have been described in the tissue immediately
surrounding the follicles, and have even been traced as far as
the follicular epithelium.
1 Von Herff, " Ueber den feineren Verlauf der Nerven im Eierstocke des
Menschens," Zeitschr. f. Oeburt. u. Gyntik., vol. xxiv., 1892. Gawronsky,
" Ueber Verbreitung und Endigungen der Nerven in den weiblichen Geni-
talien," Arch. f. Qjndk., vol. xlvii., 1894. Kallius, " Nervendigungen in
Driisen d. Eierstocke," Merkel and Bonnet's Ergeb. d. Anat. u. Entivick.,
vol. iv., 1895. Mandl, " Ueber Anordnung und Endigungsweise der Nerven
im Ovarium," Arch. f. Gynak., vol. xlviii., 1894-5. Vallet, " Nerfs d'Ovarie,"
&c.f Thesis, Paris, 1900. Abel and Mcllroy, " Nerves of the Ovary,"
Phys. Soc., June 5th, 1909. See also references on p. 329.
2 Rouget, " Recherches sur les Organes Erectiles de la Femme," Jour, de
la Phys., vol. i., 1858.
THE FEMALE GENERATIVE ORGANS 527
THE INNERVATION OF THE UTERUS AND VAGINA AND THE
MECHANISM OP UTERINE CONTRACTION
It is well known that the onset of parturition is manifested
by rhythmically repeated contractions of the uterus which
constitute the " labour pains/' But although the contractions
are most pronounced at this period, observations on animals
have shown that even in a virgin uterus rhythmical movements
may occur.
Kehrer l showed long ago that a uterus separated from the
body is capable of undergoing contractions if kept moist, and
at the normal body temperature. More recently Helme,2
Kurdinowski,3 Franz,4 and others have confirmed Kehrer 's
observation, thus proving that the movements are not dependent
on impulses received from the central nervous system. Those
investigators showed that the excised uterus may undergo
regular contractions for a prolonged period if placed in a warm
bath of normal saline solution or on having its vessels perfused
with Locke's solution. According to Franz the excised virgin
uterus exhibits no spontaneous contractions, but Helme and
Kurdinowski state that they may occur, but that they are
much weaker than those taking place during and after pregnancy.
The movements of the uterus have lately been more fully
investigated by Cushny,5 who has carried out a large number of
experiments upon rabbits and other animals. This author
states that in virgins the unexcised uterus may remain motion-
less for a long time, but that after manipulation or exposure to
air rhythmic contractions are often developed. He is disposed
to believe, therefore, that the virgin uterus in the intact animal
1 Kehrer, " Zusammenziehungen der glatten Genitalmuskelatur," &c.,
Beitrdge zur Vergl. u. Exper. Geburtskunde, 1867.
2 Helme, " Contributions to the Physiology of the Uterus and the Phy-
siological Action of Drugs upon it," Reports of the Laboratory of the Royal
College of Physicians, Edinburgh, vol. iii., 1891.
3 Kurdinowski, " Physiologische und pharmakologische Versuche an der
isolirten Gebiirmutter," Arch. f. Anat. u. Phys., phys. Abth. (supplement)
1904.
4 Franz, "Studien zur Physiologic des Uterus," Zeitschr. f. Geburt. u.
Gynak., vol. liii., 1904.
5 Cushny, "On the Movements of the Uterus," Jour, of Phys., vol. xxxv.
1906.
528 THE PHYSIOLOGY OF REPRODUCTION
undergoes no spontaneous movements. In animals in a state
of " heat/' and during and after pregnancy, spontaneous con-
tractions could generally be discerned from the first, and the
author is doubtful if the organ ever resumes its original inert
condition after it has once been pregnant. In some cases the
movements seemed to occur almost simultaneously throughout
the entire organ, but in others the circular muscle fibre con-
tracted independently of the longitudinal, and vice versa.
Mechanical or electrical stimulation caused very powerful
contractions, but these were elicited more easily in the pregnant
than in the virgin uterus, while the increased irritability was
found to persist after pregnancy was over.
Helme stated that a shutting off of the blood-supply in the
excised and perfused uterus of the sheep brought about con-
traction. Kurdinowski, on the other hand, found that in the
intact animal the opposite effect was produced. Cushny's
experiments for the most part confirm those of Kurdinowski,
but clamping the aorta in the cat led to conflicting results, since
in two cases it was succeeded by relaxation and in three
by contraction. No reason could be assigned for this diver-
gence.
It has long been known that uterine contractions can be
induced by nervous stimulation. Thus Serres l showed that
irritation of the spinal cord in the lumbar region excited the
uterus to contract, and later investigators have obtained
similar results.2 Rohrig 3 showed that asphyxia which may
bring about uterine contractions (and abortion in the preg-
nant condition) cannot do so if the lumbar cord is destroyed.
Frankenhauser 4 and Korner 5 discovered that the efferent
nerve fibres left the lumbar region of the spinal cord, and after
traversing the sympathetic, the inferior mesenteric ganglia and
1 Serres, Anatomie Comparee du Cervea, 1824.
2 Budge, " Ueber das Centrum genitospinale des Nervus sympatheticus,"
Virchoiv's Archiv, vol. xv., 1858. Riemann, "Einige Bemerkungen iiber
die Innervation der Gebarmutter," Arch.f. Gynak., vol. ii., 1871.
3 Rohrig, " Experimentelle Untersuchungen iiber die Physiologie der
Uterusbewegung," Virchow's Archiv, vol. Ixxvi., 1879.
* Frankenhauser, " Die Bewegungsnerven der Gebarmutter," Jenaische
Zeitschr.f. Med., vol. i., 1864.
5 Korner, Studien d. Phys. Instituts zu Breslau, 1865.
THE FEMALE GENERATIVE ORGANS 529
the aortic plexus, made their way to the uterus. Langley l
found that the majority passed to this organ by way of the
sympathetic in the region of the fourth, fifth, and sixth lumbar
ganglia, so that they probably arise from the third, fourth^ and_
fifth spinal nerves. Subsequently Langley and Anderson 2
showed that stimulation of the second, third, fourth, and fifth
lumbar nerves (in cats and rabbits) causes pallor and con-
traction of the Fallopian tubes, uterus, or vagina, but that
stimulation of the first and sixth lumbar nerves produces no
effect. They state that the efferent fibres are motor for the
muscular walls and vaso-constrictor for the small arteries.
The effect on the uterus and vagina was found to vary with the
state of the uterus in regard to parturition. Langley and
Anderson state that the sacral nerves send neither motor nor
inhibitory fibres to any of the internal generative organs, thus
differing from Kehrer, Korner, and others, who say that they
obtained contraction of the uterus on stimulating these nerves.
Keiffer 3 also independently investigated the innervation of
the uterus, and the results obtained by exciting various nerves,
his observations agreeing for the most part with those of Langley
and Anderson.
Cushny, in the paper already referred to, has described at
some length the effects of hypogastric stimulation, which pro-
duced in the rabbit powerful contraction of the whole uterus
irrespective of its condition in regard to the occurrence of
pregnancy. If the stimulation was prolonged for more than
fifteen seconds the organ remained in a state of extreme con-
traction (tetanus uteri), but oscillations soon began again, and
a gradual relaxation followed. Cushny shows also that the
hypogastric contains inhibitory fibres, and in one exceptional
case (a pregnant rabbit) stimulation of this nerve induced pure
inhibition, the uterus ceasing to contract at all. Moreover, in
the virgin cat the effect of hypogastric stimulation was in-
hibitory, the organ undergoing relaxation. On the other hand,
in the cat during pregnancy, or as a general rule after pregnancy,
hypogastric stimulation led to strong and immediate contraction
1 Langley, loc. cit.
2 Langley and Anderson, loc. cit.
3 Keiffer, Recherches sur la Physiologic de V Uterus, Bruxelles, 1896.
2L
530 THE PHYSIOLOGY OF REPRODUCTION
just as in the rabbit. It is supposed, therefore, that the in-
hibitory fibres prevail in the virgin, but that during and after
pregnancy the action of the motor fibres conceals their presence.1
Fellner 2 states that the " nervi erigentes " are motor for
the longitudinal muscles of the uterus and for the circular
muscles of the cervix, but are inhibitory for the circular muscles
of the uterus and the longitudinal muscles of the cervix.
According to the same author the hypogastric nerves are
motor for the circular muscles of the corpus uteri and for the
longitudinal muscles of the cervix, but are inhibitory for the
longitudinal muscles of the uterus and for the circular muscles
of the cervix.
Dembo 3 has described a peripheral nerve centre for the
uterus in the upper part of the anterior wall of the vagina in
the rabbit. Stimulation of this centre produced a very dis-
tinct contraction of both uterine cornua.
According to Jacob 4 there is an inhibitory centre for uterine
contraction situated in the medulla oblongata. This assertion
is based on experiments upon rabbits, in which it was found
1 Cushny deals also with the action of various drugs on the uterus, and
for an account of this subject the reader is referred to his paper (loc. cit.).
See also Dale, " On Some Physiological Actions of Ergot," Jour, of Phya.,
vol. xxxiv., 1906. The effects of temperature upon uterine contraction were
first described by Runge (M.) (" Die Wirkung hoher und neidriger Tempera-
turen auf den Uterus," Arch. f. Qyndk., vol. xiii., 1878), who found that hot
water caused increased contraction followed by paralysis, while cold water pro-
duced tetanus. Helme (loc. cit.) obtained results which were mostly similar.
Kurdinowski also found that cold excited contraction to tetanus, and that
long-continued mechanical stimulation produced exhaustion. Asphyxia did
not cause contraction, and experimental anaemia had no effect.
2 Fellner, " Ueber die Bewegungen und Hemmungsnerven des Uterus,"
Arch.f. Qyndk., vol. Ixxx., 1906. Labhardt (" Das Verhalten der Nerven in
der Substanz des Uterus," Arch.f. Qyndk., vol. Ixxx., 1906) describes an
extensive system of nerves in the uterus of Man and of the rabbit, the main
trunks lying between the middle layer of muscles and giving off intra-
fascicular bundles. Keiffer (Bull. Soc. d'Obstet., Paris, 1908, Nos. 2 and 3)
describes sympathetic ganglia in the uterine and vaginal walls in the course
of the large nerves coming from the hypogastric plexus.
3 Dembo, " Zur Frage iiber" die Unabhangigkeit der Kontraktinen der
Gebarmutter von dem Cerebrospinalnervensystem," Abstract in Biol. Cen-
tralbl., vol. iv., 1885. (The original is in Russian.)
4 Jacob, "Ueber die Rhythmischen Bewegungen des Kaninchenuterus,"
Verhandl. der Phya. Qesell. zu Berlin, Anat. f. Anat. u. Phys., phys. Abth.,
1884.
THE FEMALE GENERATIVE ORGANS 531
that stimulation of the medulla caused the movements of the
uterus to cease. Moreover, it is to some extent borne out by
the fact that the " pains " of labour can often be inhibited by
emotions and other contemporary actions of the central nervous,
system (see below, p. 539).
It is well known that uterine contraction can be induced by
the presence of a foreign body in the uterus, by injections into
the rectum, by the application of the child to the breast, and
by various other means. According to Kurdinowski l the
sensation of any violent pain may cause uterine contraction in
animals, and the organ may respond to remote stimulation
(e.g. in the ears). These observations alone are sufficient to
show that the contraction is often a reflex act. The experimental
evidence cited above shows no less clearly that the controlling
centre is in the lumbar portion of the spinal cord. Nevertheless
there are many indications, as just mentioned, that the move-
ments of the uterus can be brought under the influence of a
higher centre situated in the brain. On the other hand, the
fact that rhythmical contractions can continue to occur in the
absence of all nervous connections is a certain proof that they
are primarily independent of the nervous system, although
normally they are to a large extent influenced by it. It must
be concluded, therefore, that the power to contract and relax
rhythmically is an inherent property of the muscular tissue of
the uterus.
The question as to the nature of the mechanism involved
in uterine contraction is inseparably connected with the further
problem concerning the part played by nervous influence in
controlling the course of parturition. This subject is dealt
with below (p. 537).
THE NORMAL COURSE OF PARTURITION IN THE HUMAN
FEMALE
The increased size of the foetus, together with the accumula-
tion of the amniotic fluid, causes the uterus towards the end of
pregnancy to become considerably distended. The enlarge-
1 Kurdinowski, " Ueber die Keflectorische Wechsel beziehung zwischen
der Brustdriisen und dem Uterus," Arch. f. Gynak., vol. Ixxxi., 1907.
532 THE PHYSIOLOGY OF REPRODUCTION
ment is still further increased by the growth of the uterine
wall itself. Partly as a consequence of this enlargement the
waves of contraction which were present at the beginning of
pregnancy, or even previously, as above described, become
much more marked, but are still unaccompanied by painful
sensation. With the onset of labour, however, these uncon-
scious painless contractions are replaced by others of increasing
intensity, and in the human subject distinctly affecting con-
sciousness and giving rise to severe suffering. These are the
" labour pains " which bring about the dilatation of the cervix
uteri and lead to the expulsion of the child followed by the
placenta.
At the commencement of labour the contractions do not
occur oftener than once every half or quarter of an hour, but
they soon become more frequent, and recur eventually at in-
tervals of two or three minutes. Their average duration is
about a minute, though actual pain is experienced for a shorter
time.1 Polaillon 8 and Schutz 3 have shown from tracings that
the period of increase occupies the main portion of the " pain/'
its acme being of short duration. In animals possessing bi-
cornuate uteri the contractions are said to be peristaltic in nature,
but this is not so evident in the case of the human subject.
Williams 4 has discussed the question as to the amount of
force exerted at each " pain " in a woman during delivery. He
states that the expenditure of energy necessary to restrain the
head of the child as it emerges from the vulva is represented by
not more than fifty pounds, although the obstetrician some-
times finds it impossible to hold it back at the acme of the pain.
Schutz 5 made an attempt to arrive at a more exact estimation
by inserting into the uterus a rubber bag connected with a
mercury manometer. He found that whereas the intra-uterine
pressure between the contractions was represented by a column
1 Williams, Obstetrics, London, 1904.
2 Polaillon, Recherches sur la Physiologic de I' Uterus Gravide, Paris,
1880.
3 Schutz, " Ueber die Formen der Wehenerven und iiber die Peristaltik
des Menschlichen Uterus," Arch. f. Gynak., vol. xxvii., 1886.
4 Williams, loc. cit.
s Schutz, " Ueber die Entwickelung der Kraft des Uterus in Verlaufe der
Geburt," Verhandl. d. Deutsch. Gesett.fur Gyndk., 1895.
THE FEMALE GENERATIVE ORGANS 533
of mercury of twenty millimetres, during the pains it rose to a
height of from eighty to two hundred and fifty millimetres.
This difference is calculated to represent a force of from eight
and a half to twenty-seven and a half pounds.
The clinical course of labour and the muscular forces con^
cerned in the process are fully dealt with in the text-books on
Midwifery,1 and it is not proposed in the present work to devote
more than a very brief space to the consideration of this subject.
It is customary to divide the period of labour into three stages.
The first stage is characterised by the dilatation of the
cervix and os uteri. Galabin gives the following account of
the mechanical processes which take place in the uterus during
this stage of labour :— ''' There are three elements in the
mechanism of dilatation of the cervix and os ; first, the
mechanical stretching by the bag of membranes ; secondly,
the contraction of the longitudinal fibres of the uterus, which
draw the cervix open ; and thirdly, the physiological relaxation
of the circular fibres, which [is always associated] with the con-
traction of the body of the uterus. It follows from the principles
of mechanics that the effect of any given pressure within the
bag of membranes in producing a tension of the edge, either of
the internal or external os, is directly proportional to the
diameter of the os, and therefore vanishes when the os is very
small. Hence, if the os is closed to begin with, some dilatation
by the stretching influence of the longitudinal fibres must have
taken place before the mechanism of dilatation by the bag of
membranes or parts of the foetus can come into play. The
mechanical action of the dilating part, as it is pressed into the
cervix, is that of a wedge ; a fluid and uniform wedge, in the
case of the bag of membranes ; a solid and irregular wedge, in
the case of the head or other part of the foetus. It follows that
the effect produced by the wedge varies according to the acute-
ness of its angle at the points where it is in contact with the edge
of the os. ... It follows that the dilating force vanishes when
there is no projection, and becomes greater the more complete
1 See Williams, loc. cit. Galabin, Manual of Midwifery, 6th Edition,
London, 1904, and the other text-books on the subject. See also Sellheim,
«' Die Physiologic der Weiblichen Geschlechtsorgane," Nagel's Handbuch der
Physiologic des Menschen, vol. ii., Braunschweig, 1906.
534 THE PHYSIOLOGY OF REPRODUCTION
is the projection. It follows also that it becomes progressively
more and more effective in proportion to the degree of dilatation
which has already been produced/' l
The second stage, which has been called the expulsive stage,
may be said to include the period from the complete dilatation
of the os uteri to the delivery of the foetus. When the os has
become fully expanded, and the membranes have ruptured,
there is generally a short lull in the pains of labour. At the
end of the lull the contractions of the uterus begin to recur with
increasing vigour and frequency, while the abdominal muscles
which are brought into play for the first time exert on the
uterus an additional extrinsic force similar to that exerted
on the rectum during defsecation. These abdominal contrac-
tions are synchronous with those of the uterus, and therefore,
like them, tend to occur rhythmically. At the commencement
of the process the patient is able to some extent to control
the contractions by an effort of the will, but later on they are
quite involuntary. The combined effect of the contractions is
to drive the child, usually head foremost, through the vagina
and then out through the vulva, these however playing a purely
passive part in the act of expulsion. Sometimes the membranes
do not rupture before birth, and the child is born surrounded
by a " caul."
The third stage of labour comprises the expulsion of the
placenta. After the delivery of the child the uterus ceases to
contract for a longer or shorter period, at the end of which its
activity is renewed once more. At this time the placenta becomes
completely separated from the wall of the uterus, and passes into
the upper part of the vagina. It is expelled thence through
the action of the muscles of the abdomen. During this stage
there is almost invariably a certain amount of haemorrhage,
which is represented in normal cases by from three to four
hundred cubic centimetres of blood.
The duration of labour shows considerable variation, but is
generally longer in primiparous women (i.e., those who have
never borne children before) than in multiparous ones. The
average for the former is rather more than eighteen hours, the
three stages respectively occupying sixteen, two, and from a
1 Galabin, loc. cit.
THE FEMALE GENERATIVE ORGANS 535
quarter to half-an-hour. The average for multiparous women
is twelve hours, eleven of which are occupied by the first, and
one by the second stage. The duration of labour in primiparous
women depends also upon age, being usually more prolonged
in elderly subjects.
PARTURITION IN OTHER MAMMALIA
In animals the process of delivery varies somewhat in the
different animals. In the horse the foetus, which has been
lying on its back during intra-uterine life, preparatory to birth
FIG. 131.— The first stage in the revolution of the equine foetus. The os is
dilated by the membranes, which have not yet ruptured. (After Franck.
From Smith's Veterinary Physiology, Bailliere, Tindall & Cox.)
changes on to its side and afterwards assumes the upright
position, with its muzzle and forelegs in the direction of the
pelvis. Dilatation of the passage follows, and the foal is de-
livered head first. In the cow and sheep the movements which
occur are essentially similar. It is stated that the alteration
in the position of the foetus is not brought about by its own
movements but by the uterine contractions. The revolution of
the foetus prior to birth in the mare and cow is apparently re-
sponsible for the torsion of the neck of the uterus and vagina
which often occurs in these animals.
Parturition in the mare is accompanied by a complete
separation of the chorion from the uterine wall. As a conse-
536 THE PHYSIOLOGY OF REPRODUCTION
quence of this fact any difficulty experienced in delivery usually
causes the death of the foal. In Ruminants, on the other hand,
the separation of the cotyledons takes place very gradually,
so that the connection between the maternal and foetal circula-
tion is maintained to some extent until the last. In these
animals the process of parturition may last for hours. In the
mare, on the contrary, delivery is usually effected very rapidly.1
The foetal membranes may be expelled with the young or be
FiG. 132. — The Foal in the normal position for delivery, the revolution being
completed and the membranes ruptured. (After Franck. From Smith's
Veterinary Physiology, Bailliere, Tindall & Cox.)
retained until a little later, when the uterus recovers its power
and then expels them.
In animals such as the rat, in which multiple conception is
the rule, the " presentation " of the young at birth may be
either " breech "or " head." The foetuses tend to be expelled
irregularly, some being discharged along with the placenta,
while others are born separately.2
1 Smith, Veterinary Physiology, 3rd Edition, London, 1907. Fleming,
Veterinary Obstetrics, London, 1878. See also Wortley Axe, "The Mare
and Foal," Jour. Royal Agric. Soc.} 3rd Series, vol. ix., 1898, and Leeney,
" The Lambing Pen," Jour. Royal Agric. Soc., 3rd Series, vol. vii., 1896.
2 Brumpt, "Parturition chez le Rat blanc," Bull. Soc. Zool., France, vol.
xxxii., 1907. The loosening of the placenta and other changes in Tupaia are
described by van Herwerden, " Die puerperalen Vorgiinge in der Mucosa uteri
von Tupaia javanica," Anat. Hefle, vol. xxxii., 1907.
THE FEMALE GENERATIVE ORGANS 537
THE NERVOUS MECHANISM OF PARTURITION
Parturition may be considered as being normally a reflex
act, the centre of which is situated in the lumbar region of the
spinal cord. On the other hand, it has been shown from experi-
ments upon animals that the transmission of impulses through
the cord is not absolutely essential to the occurrence of par-
turition.
Simpson (Sir James) x removed the spinal cord from the first
dorsal vertebra downwards from a number of sows a few days
before parturition was due. Some of the animals died as a
result of the operation, but in others parturition proceeded
normally, excepting that in each case the last foetus of the
series was not born. ' The uterine contractions proceeding
from fundus to cervix were sufficient to expel the foetuses from
the uterus ; and each foetus as it came into the vagina was
thence extruded by the force transmitted from the foetus behind
it ; but when the last foetus came into the vagina it remained
there, because there was nothing to transmit the uterine ex-
pulsive force, while the vaginal and abdominal muscles, being
under the influence of the spinal nerves, had been rendered
powerless by the removal of the spinal cord."
Riemann 2 states that after the destruction of the cord of a
cat from the third dorsal vertebra downwards the animal gave
birth to a kitten two days subsequently, shortly before its death.
Rein 3 describes experiments upon rabbits in which he
severed the uterus from all nervous connection with the cerebro-
spinal system, and found afterwards that the mechanism of
labour was not destroyed.
Furthermore, Oser and Schlesinger,4 as a result of experi-
mental evidence, state that parturition can occur in animals
after the severance of the sympathetic nerves which pass to
the uterus, but it is difficult to understand how this operation
1 Simpson, Selected Obstetric Works, edited by W. H. Black, Edinburgh, 1871.
2 Riemann, " Einige Bemerkungen iiber die Innervation der Gebar-
mutter," Arch. f. Gyncik., vol. ii., 1871.
3 Rein, "Beitrag zur Lehre von der Innervation des Uterus," Pflnger's
Archiv, vol. xxiii.
4 Oser and Schlesinger, " Experimented Untersuchungen iiber Uterus-
be wegungen," Strieker's Med. Jahrbilcher, 1872.
538 THE PHYSIOLOGY OF REPRODUCTION
could have been made complete without interfering with the
blood supply to that organ.
More recently, Goltz and Ewald l have described an experi-
ment in which they completely exsected the spinal cord of a
bitch from the mid-dorsal region downwards, and found that
after the operation the animal experienced normal " heat/'
became pregnant, and in due course produced a litter of pups.
Kruiger and Oflergeld 2 have also shown that parturition is
possible after destruction of the cord. Goltz had already
shown 3 that parturition could occur after the transection of
the spinal cord in the dorsal region, and consequently after all
connection with the higher centres had been cut oft. (See pp.
490-491.)
The last-mentioned fact is also demonstrated in the various
cases in which parturition has proceeded normally in women
suffering from paraplegia from the level of the mid-dorsal part of
the spinal cord downwards. Routh 4 has recorded several such
cases, and in all of them labour set in and proceeded regularly
(or almost regularly), but without sensation. In Routh 's own
patient the injury was in the dorsal region of the cord, which
was completely disorganised at the seat of the fracture of the
spine, as the post-mortem evidence -showed. In the lumbo-
sacral region, however, there were a large number of cells which
were normal in appearance, so that it could not be contended
that the centre for parturition had been destroyed. Routh also
refers to Brachet's case,5 which he states is the only one re-
corded in which the spinal lesion was apparently in the lumbar
region of the cord. In this case the uterus failed to make the
normal contractions, and the child was eventually extracted
with forceps. The placenta also had to be removed by hand.
1 Goltz and Ewald, " Der Hund mit verktirztem Riickenmark," PjHiger's
Archiv, vol. Ixiii., 1896.
2 Kruiger and Offergeld, " Der Vorgang von Zeugung, Schwangerschaft,
Geburt, und Wochenbett an der ausgeschalteten Gebarmutter," Arch. f.
Oyndk., vol. Ixxxiii., 1908.
3 Goltz, "Ueber den Einfluss des Nervensystems auf die Vorgange
wahrend der Schwangerschaft und des Gebarakts," Pfluger's Archiv, vol. ix,,
1874.
4 Routh, "Parturition during Paraplegia," Trans. Obstet. Soc., Lond.,
vol. xxxix., 1898.
5 Brachet, Recherches, 2nd Edition, Paris, 1837.
THE FEMALE GENERATIVE ORGANS 539
It is clear, therefore, that a spinal lesion in the lumbar region
may result in materially weakening the action of the uterus,
and so may hinder the normal course of labour. On the other
hand, in those cases in which the lesion was in the dorsal part of
the cord, the possibility of spinal reflexes in the lumbar region
could not be excluded.1
The following general conclusions regarding the nervous
mechanism of parturition are based largely on those of Routh.
(1) The act of parturition is partly automatic and partly reflex,
these actions corresponding in the main to the first and second
stages of labour respectively, the spinal reflexes usually com-
mencing as soon as the membranes have ruptured. (2) Direct
communication with the brain is not essential for the proper
co-ordination of uterine action, but the brain appears to exercise
a controlling influence of some kind. Thus, emotions often
become a hindrance to the progress of parturition. It would
seem possible that this inhibition of uterine contractions
is brought about by an inhibition of a centre in the brain
(see above, p. 530). (3) Direct communication between the
uterus and the lumbar region of the cord, is generally essential
for the occurrence of those rhythmical contractions which take
place during the progress of normal labour. There is experi-
mental evidence upon animals, however, that the uterus is some-
times able automatically to expel its contents, at least as far
as the relaxed portion of the genital cord, even when entirely
deprived of all spinal influence.2
CHANGES IN THE MATERNAL ORGANISM
The influence of parturition upon the metabolism of the
maternal organism is dealt with by Sellheim.3 There is a
1 Routh also discusses post-mortem parturition, but points out that in
most of those cases where it occurred, the expulsion of the foetus was caused
by increased abdominal pressure due to putrefactive gaseous distension
during a condition of muscular relaxation. There are some facts which
go to prove that uterine contractility and retraction may continue or even
commence after death, possibly resulting from the movements of the
imprisoned child.
2 For further references to the literature of the nervous mechanism of
parturition, see Bechterew, Die Funktionen der Nervencentra, Weinberg's
German translation, vol. i.f Jena, 1908. 3 Sellheim, loc. tit.
540 THE PHYSIOLOGY OF REPRODUCTION
slight rise of temperature during the process, and the pulse rate
is also affected, being much quicker during the pains, but slower
between them, the difference amounting to as much as thirty-
six beats a minute. The blood shows a marked leucocytosis,
and the blood pressure is higher. Urine is secreted in smaller
quantities, and is liable to contain traces of renal epithelium,
red and white blood corpuscles, and albumen.
THE CAUSE OF BIRTH
Foster in his Text-book of Physiology l has written as
follows : " We may be said to be in the dark as to why the
uterus, after remaining for months subject only to futile contrac-
tions, is suddenly thrown into powerful and efficient action, and
within it may be a few hours, or even less, gets rid of the burden
which it has borne with such tolerance for so long a time. None
of the various hypotheses which have been put forward can be
considered as satisfactory. We can only say that labour is
the culminating point of a series of events, and must come
sooner or later, though its immediate advent may sometimes be
decided by accident/'' What. Foster wrote about this question
is still true to-day, for no real progress has been made towards
the solution of the physiological problem as to the immediate
cause of parturition.
Williams 2 has classified the various theories which have
been formulated under eleven heads. These may now be
briefly considered in the order adopted by him.
(1) The increasing irritability of the uterus, as manifested by
its greater tendency to respond to stimulation in the later
stages of gestation, is probably a factor in determining the
time of birth. As already described, the uterine contractions
towards the close of pregnancy are not only more frequent, but
they are also much more intense. This growing irritability is
no doubt to be directly associated with the increase in the size
of the foetus.
(2) It is suggested that the mere distension of the uterus
must, after a certain point, lead to a reaction, when the organ
1 Foster, Text-Book of Physiology, 5th edition, vol. iv., London, 1891.
2 Williams, loc. cit.
THE FEMALE GENERATIVE ORGANS 541
attempts to reduce itself to its former size, and so expels its
contents. This idea receives some support from the fact that
twin pregnancies and hydramnios (or the presence of an
excessive quantity of liquor amnii) often result in premature
labour.
(3) It has been supposed from early times onwards that
parturition might be brought about through the pressure of the
foetus producing a gradual dilatation of the cervix. Williams,
however, has pointed out that this condition of the cervix
cannot be the sole factor, since in a certain number of cases,
especially in twin pregnancies, a pronounced dilatation has
been known to occur for a considerable period prior to the
onset of labour.
(4) Keilmann,1 working upon the bat, came to the conclusion
that the onset of labour was caused by the increasing pressure
set up by the lower distended portion of the pregnant uterus
(the lower uterine segment) upon the surrounding nerve ganglia.
Supposing this conclusion to be correct as applied to the bat, it
is not quite clear that it is equally applicable to the human
female and to other animals.
(5) Simpson 2 and others were of opinion that the " pains "
of labour were the indirect result of a partial separation of
foetus and decidua, brought about by the fatty degeneration of
the latter in the last stages of pregnancy, so that the foetus
became virtually converted into a foreign body, which caused
the uterus to respond accordingly. It is no doubt true that
part of the maternal placenta undergoes degenerative changes
towards the end of pregnancy, but there is no evidence that
this by itself is sufficient to cause a separation of the foetus from
the uterine wall.
(6) There is no evidence in support of the theory that the
exciting cause of parturition is an accumulation of carbon
dioxide in the blood, beyond the fact demonstrated by Brown-
Sequard,3 Keiffer,4 and others, that uterine contractions can be
induced experimentally by this means.
1 Keilmann, " Zur Klarung der Cervixfrage," Zeitschr.f. Oeb. u. Gynak.,
vol. xxii., 1891. 2 Simpson, loc. cit.
3 Brown-Sequard, Experimental Researches, English translation, London,
1853. 4 Keiffer, loc. cit.
542 THE PHYSIOLOGY OF REPRODUCTION
(7) Spiegelberg l put forward the theory that parturition
was brought about through the action of substances secreted by
the foetus and passed into the maternal blood. These. hypo-
thetical substances, which appear to have been comparable to
Starling's hormones, were supposed to act on the uterine centre
in the spinal cord. Spiegelberg suggested, further, that the ex-
citing substances were elaborated as a result of an insuffi-
ciency of nutrition, and were an indication that the mature
foetus required other sustenance than that supplied to it
through the placenta. This theory appears to be devoid of all
experimental basis, but it is not opposed by any of the known
facts.
(8) Tyler Smith,2 Minot,3 Beard 4 and others have held the
view that there is a connection between parturition and men-
struation, the two processes being physiologically homologous.
According to this theory, there is an increased tendency towards
uterine contractions at the periods at which menstruation would
occur if the condition were not one of pregnancy. Thus Tyler
Smith says that there is in all women a greater tendency to
abort at the times represented by the catamenial periods.
According to Minot, the menstrual and gravitidal changes follow
the same cycle of events, the pregnant uterus passing through
a prolonged and intensified " menstrual cycle/' Consequently,
it is probable that there is a common cause for the ending of
the series (the casting off of the superficial part of the mucosa
in both cases). This theory has been further elaborated by
Beard, who has arrived at the conclusion that parturition takes
place at the time it does in order that a new ovulation may be
carried into effect. .This author lays great stress upon the
rhythmical character of the sexual processes, and points out
in support of his theory that " heat " and ovulation frequently
ensue shortly after parturition. That this does not happen in
many animals has been already shown in the second chapter of
1 Spiegelberg, " Die Dauer der Geburt," Lehrbuch der Oeburtshulfe, vol. ii.
1891.
2 Tyler Smith, Parturition and the Principles and Practice of Obstetrics,
London, 1849.
3 Minot, " Uterus and Embryo," Jour, of Morph., vol. ii., 1889. " Human
Embryology."
4 Beard, The Span of Gestation and the Cause of Birth, Jena, 1897.
THE FEMALE GENERATIVE ORGANS 543
this work.1 Moreover, Beard's theory makes no attempt to
explain why parturition should occur in some animals at the
close of one particular ovulation interval (e.g. in the human
species at the close of the tenth), and in other animals at the
termination of a different one (that is to say, no explanationTs
given of the variation in the number of ovulation intervals
which are comprised in the period of gestation in different
animals). It cannot be said, therefore, that Beard's hypothesis
as to the time occupied by gestation and the cause of birth is
an adequate one.
(9) Various writers, such as Geyl,2 have laid some stress
upon the belief that parturition occurs in women at a time
which has proved, after long ages, to be the most suitable for
the perpetuation of the race. A similar statement might of
course be made about any other existing species of mammal,
for it is only another way of stating the generally accepted
belief that parturition, like all other natural phenomena in the
animal world, is under the control of natural selection. In
support of this contention, as applied to the human species, it
has been pointed out that when labour takes place after an
abnormally prolonged gestation, it frequently results in dead
children, while, on the other hand, premature labour results in
puny, ill-developed children, who often perish in early life.
(10) Eden,3 and also Williams, have pointed out " that the
frequent occurrence of infarct formation [i.e. a certain kind of
degenerative change] in the placenta at term must be regarded
as evidence of its senility, and that this change is analogous
to the obliteration and atrophy of the chorion laeve at an earlier
period. Where these changes are marked the nutrition of the
foetus must be interfered with, and it is possible that certain
of its metabolic products may result in stimulation of the
uterine centre." * This theory should be compared with that
advanced by Spiegelberg (see above).
1 Beard holds that ovulation takes place shortly after parturition in all
Mammals. This is not the case in any moncestrous animals which have a
prolonged anoestrous period.
2 Geyl, "Ueber die Ursache des Geburtseintrittes," Arch. /. Qyncik.,
vol. xvii., 1881.
:i Eden, " A Study of the Human Placenta," Jour, of Path, and Bacterial.,
vol. iv., 1897. 4 Williams, loc. cit.
544 THE PHYSIOLOGY OF REPRODUCTION
(11) Lastly, Williams calls attention to the fact that ex-
cessive physical fatigue, sudden jars or violence, mental emotion,
fright, &c., may lead to the termination of gestation in women.
Similarly, it is well known that circumstances of a like nature
may induce abortion in animals.
Williams remarks that in all probability the onset of labour
in most cases is due to a combination of a number of the
above-mentioned causes. The main objection to all the
theories which have so far been advanced is that they take no
account of the complexity of the problem. An hypothesis may
be fairly adequate as a general explanation of the duration of
gestation, while at the same time taking no account of the
immediate cause of birth. Thus, it is no doubt true that the
time of parturition is determined largely by the necessities
of the offspring, but this conclusion provides no sort of ex-
planation as to why it is that the pains of labour in any one
particular species generally commence at a certain fixed stage
of development, and it remains for us to assume that it is one
of the inherent properties of the uterus in the species in question
that they should do so. Even on this assumption it is im-
possible to avoid concluding that there must be some definite
exciting cause, such as that postulated by Spiegelberg.
PROLONGED GESTATION
The duration of gestation in any one species usually varies
within quite narrow limits, but under exceptional circumstances
it may continue for an abnormally long period. Thus, Williams l
records a case of a woman with whom pregnancy extended for
over eleven lunar months after the cessation of menstruation,
instead of the usual ten lunar months (i.e. about 280 days). In
this case typical labour pains were experienced at the end of
the tenth month, but these subsided after a short time, and
were not renewed until four weeks later, when they resulted in
parturition. The same woman became pregnant a second time,
when the period of pregnancy was again prolonged until the
end of the eleventh month after the last menstruation. The
children on each occasion were abnormally large and heavy
1 Williams, loc. cit.
THE FEMALE GENERATIVE ORGANS 545
at birth. Allen l has recently recorded a number of further
cases of prolonged gestation in women, the longest time
chronicled being 334 days. It is stated that inertia of the
uterus (due to fatty degeneration) is frequently associated
with prolonged gestation ; but the occurrence of the latter is
no doubt often brought about by other causes which are at
present unknown.
Cases of prolonged gestation have been observed also among
animals. Professor Ewart has informed the writer of a mare
in his possession in which the period of gestation was extended
to twelve months instead of the usual eleven. Other cases of
prolonged gestation in mares, and also in cows, have been re-
corded by Tessier 2 and Franck-Albrecht-Goring,3 and appear
to be not uncommon. No satisfactory reason has been sug-
gested to account for such cases.
According to Pinard 4 prolonged gestation may occur in
Rodents (Dipodillus simoni, Meriones shawi, M. longifrons, Mus
musculus, &c.), as a result of suckling a large litter produced
just previously to a second gestation, the development of
the young during the latter being arrested by a relative
insufficiency of nourishment. In some cases the period of
gestation was half as long again as the normal duration.
THE PUERPERTUM
In multiparous women the uterus continues to contract
and relax at more or less regular intervals after the expulsion of
the placenta which marks the termination of the third stage of
labour. The contractions which occur at this period give rise
to the sensations commonly known as the " after-pains/' These
may last several days, but are not generally very severe after the
first day. They are particularly liable to occur when the child
1 Allen (L. M.), "Prolonged Gestation," Amer. Jour, of Obstet., vol. lv.,
1907.
- Tessier, "Recherches sur la Duree de la Gestation," &c., Mem. de I'Acad.
des Sciences, Paris, 1817.
3 Franck-Albrecht-Goring, "Die Trachtigkeitsdauer," Thierdrztliche Oe-
burtshulfe, vol. iv., 1901.
•* Pinard, Article "Gestation," Richet's Dictionnaire de Physiologic,
vol. vii., Paris, 1905.
2M
546 THE PHYSIOLOGY OF REPRODUCTION
is put to the breast, a fact which seems to indicate a nervous
connection between the uterus and the mammary glands.
In primiparous women the tonicity of the puerperal uterus is
usually greater than in multiparous ones, so that the uterus is
capable of remaining during this period in a state of almost
uninterrupted retraction unless blood clots or other foreign
bodies are present in the cavity, in which case the organ under-
goes movements in attempting to expel them.
This tonic retraction of the uterus is. an important factor in
closing the blood sinuses, and so preventing bleeding. If, owing
to any circumstance, the normal contraction and retraction of
the uterus are interfered with, post-partum haemorrhage is
liable to occur. This is not infrequently the case with white
women who have migrated to the tropics, or with ill-nourished
women in the slums, in whom, owing apparently to an inefficiency
in the uterine nerve supply, the organ tends to become inert.1
It follows from what has been said that multiparous women
are more liable to post-partum haemorrhage than primiparous
ones.2
According to Longridge the anaemic condition of the normal
puerperal uterus is due partly to the effacement of the ovarian
and uterine arteries which occurs when the uterus contracts.
' The reality of this occurrence is supported by an observation
which can be made in many cases of Caesarian section ; in this
operation it is noticed that as long as the uterus remains outside
the abdomen it tends to bleed, but that as soon as it is dropped
back bleeding ceases. It is not the warmth of the abdominal
cavity that checks the bleeding, since it may continue when the
uterus is wrapped in warm towels outside the abdomen. But
the mere fact of pulling up the uterus opens out the concertina,
as it were, and allows blood to flow through the arteries. If
the bladder is full at the end of labour, the uterus is pushed
1 Longridge, The Puerperium, London, 1906.
2 Longridge has pointed out, however, that the amount of post-partum
discharge in multiparae is not as a rule in proportion to the severity
of the "after-pains," and consequently that the latter cannot be ascribed
simply to defective retraction on the part of the uterus. He suggests,
therefore, that the " after-pains" in multiparae are largely due to the uterus
suffering from cramp resulting from the excessive exertion involve4 in dis-
charging the child.
THE FEMALE GENERATIVE ORGANS 547
upwards, and slight loss may continue until the water is drawn
off. As soon as the uterus is allowed to nestle down into its
normal position the bleeding stops." l
The puerperal vaginal discharge is known technically as the
lochia. It varies considerably in amount in different individuals,
and changes in character as the puerperium proceeds, ceasing
altogether about the middle of the third week. For the first few
days it consists almost entirely of blood, which makes its way
from the raw surface of the uterus and from lacerations caused
during delivery. This is the lochia rubra. After three or four
days it becomes paler, owing to the dilution of the sanguineous
discharge by mucous secretion. This is called the lochia serosa.
During the next three days the normal colour of the lochia is
brown. This change (from pale pink to brown) is due to the
fact that the normal acidity of the vaginal secretion has by this
time become re-established. Longridge suggests that the
brown colour is probably the result of the formation of some
such compound as acid hsematin. After about the tenth day
the lochia assumes a whitish or yellowish-white colour, owing
to the admixture of leucocytes and the cessation of the blood
flow. It is then known as the lochia alba. In many cases,
however, traces of blood may be observed for weeks, but the
lochia alba consists mainly of secretions from the vagina and
cervix, together with leucocytes, a few epithelial cells, fragments
of decidual tissue, and crystals of cholesterin. Micro-organisms
are also present in the discharge, but recent investigations have
shown that the lochia obtained directly from the uterine cavity
does not contain bacteria, excepting in cases where the uterus
is the seat of infectious processes.2
The average quantity of the discharge has been computed by
Gassner 3 at 1485 cubic centimetres, or about 50 ounces. Giles 4
estimated it as 10 J ounces (or considerably less than Gassner Js
1 Brock (Practitioner, January 1908) has recently expressed the opinion
that puerperal bleeding is chiefly venous, pointing out that the discharge is
usually very dark in colour.
2 Krb'nig, Bakteriologie des Genitalkanales, &c., Leipzig, 1907.
3 Gassner, "Ueber die Veranderungen des Korpergewichtes bei Schwang-
eren, Gebarenden, und Wochnerinnen," Monatsschr. f. Geburtskunde,vol. xv.,
1862.
4 Giles, " On the Lochia," Trans. Obstet. Soc., vol. xxxv., 1897.
548 THE PHYSIOLOGY OF REPRODUCTION
estimation), and found further that in women who were
accustomed to bleed freely at the menstrual periods the amount
of the lochial discharge was beyond the average. According
to Gassner, the discharge is generally less in women who suckle.
The uterus after delivery becomes rapidly reduced in size.
This process is known as the involution of the uterus ; it is
completely effected in from five to eight weeks, the greatest
reduction taking place in the first few days. Thus the freshly
delivered uterus weighs on an average 1000 grams (or about
2 pounds), a week later it weighs only half that amount, at
the close of the second week 375 grammes, and at the end
of the puerperal period as little as 60 grammes (or about 2
ounces). Its decrease in size is such that by the tenth day
after parturition the organ is once more confined to the cavity
of the pelvis proper, and cannot be felt above the symphysis.
The process of uterine involution is the result chiefly of
changes occurring in the muscle walls.1 The size of the in-
dividual cells becomes very markedly diminished, but there is
little or no reduction in their number. Fatty degeneration does
not take place in the muscular tissue. It is stated that the
retraction of the muscle fibres produces a compression of the
vessels, and that the comparatively anaemic condition of the
puerperal uterus, especially in the earlier stages, is due to this
cause. Subsequently the uterus becomes more vascular again.
The remains of the decidua which are not expelled at partu-
rition undergo degeneration and are discharged in the lochia,
leaving only the fundi of the glands and a certain amount of con-
nective tissue from which the uterine stroma is renewed. The
epithelium is re-formed from that of the glands, as shown by
Friedlander,2 Kundrat and Engelmann,3 Leopold,4 Kronig,5
1 The account given of the changes in the uterus during the puerperium
is based largely on that given by Williams (Obstetrics, New York, 1904).
See also Sellheim, " Das Wochenbett," in Nagel's Handbuch der Physiologic
des Menschen, vol. ii., Braunschweig, 1906, where further references are given.
2 Friedlander, Physiologische und Anatomische Untersuchungen iiber den
Uterus, Leipzig, 1870.
3 Kundrat and Engelmann, " Untersuchungen iiber die Uterusschleim-
haut," Strieker's Med. Jahrbuch, 1873.
4 Leopold, Studien iiber die Uterusschleimhaut, &c., Berlin, 1878.
s Kronig, " Beitrag zum anatomischen Verhalten der Schleimhaut der
Cervix und des Uterus," &c., Arch. f. Gynak., vol. Ixiii., 1901.
THE FEMALE GENERATIVE ORGANS 549
and others.1 Excepting in the position of the placenta, the
new epithelium is completely regenerated by the end of the
sixth week after delivery.
The placental area at the end of parturition is marked— by_
the presence of thrombosed vessels. It is raised above the
general surface of the uterine wall, and is irregular in shape. It
very soon diminishes in size, its diameter being not more than
two centimetres long at the end of the puerperal period, although
its former position may be detected as an area slightly stained
by blood pigment for several months after delivery.
Williams states that in the last month of pregnancy some of
the sinuses at the placental area undergo thrombosis, but that
this process becomes much more marked after the completion
of labour, although many of the sinuses are simply compressed
by the contracting uterine muscles without ever becoming
thrombosed.2 The thrombi are eventually converted into
ordinary connective tissue by a cellular proliferation from
the lining membrane of the vessels. While this change is in
progress the lining membrane presents a folded appearance
somewhat resembling a typical developing corpus luteum.
This is especially well seen about the fourth week after parturi-
tion, but even up to the end of a year the convoluted appearance
is still sometimes discernible.3
The lumina of the arteries become reduced in size, but the
thickening of their walls, which takes place during pregnancy, is
an alteration of a more permanent character. This histological
change affords a means of discriminating between a virgin and
a parous uterus.
The cervix uteri remains for some time after delivery as a
soft, flaccid structure with lacerated edges, but it gradually
undergoes involution, the lumen becoming narrower. The
vagina takes about the same time to recover as the uterus.
1 Leusden, assuming the syncytial tissue of the deciduurn to be of maternal
origin, has suggested that it may assist in giving rise to the new epithelium
(" Ueber die Serotinalen Riesenzellen," &c., Zeitschr. f. Oeb. und Gynak.,
vol. xxxvi., 1897).
2 According to Longridge (see below in the text), thrombosis is of little
or no importance in assisting the hsemostasis of normal labour.
3 Williams (Sir J.), "Changes in the Uterus," &c., Trans. Obstet. Soc.,
vol. xx., 1878. See also Helme, "Histological Observations," &c., Trans.
Roy. Soc. Edin., vol. xxxv., 1890.
550 THE PHYSIOLOGY OF REPRODUCTION
FlG. 133.— Virginal exter-
nal os (human). (From
Williams' Obstetrics,
Appleton & Co. )
After a first delivery its outlet remains permanently wider than
before. The rugse reappear about the third week. The place
of the hymen is taken by numerous small tags of tissue which
become transformed into the carunculae myrtiformes. The
condition of the labia majora and
labia minora is generally flabby and
atrophic as contrasted with that exist-
ing in virgin women.
The characteristic changes which
occur in the breasts in connection
with the secretion of milk are described
in the next chapter.
The quantity of urine passed during
the first two days of the puerperium is
generally above the average. The urine
frequently contains sugar, which may be either glucose or lactose.
In the latter case it is generally believed that the sugar has been
absorbed into the circulation from the changed mammary glands.
When glycosuria occurs, it is probably comparable to post-opera-
tive glycosuria (see p. 510 and pp. 571—573). Albumen may
also be present in the urine in the first
days of the puerperium. It is stated
further that there is an increase in the
amount of acetone 1 (see also p. 507).
As mentioned above, a marked leuco-
cytosis occurs during labour. According
to Hofbauer,2 this becomes still more
pronounced during the first twelve
hours of the puerperium, after which
the number of leucocytes in the blood
falls again and in a short time becomes
normal. Henderson 3 states that on the
fifth day the average number of leucocytes per cubic millimetre is
12,000, whereas immediately after parturition it is 21,000, as
1 Scholten, " Ueber Puerperale Acetonurie," Hegar's Beitrdge zur Oeb.
und Gyncik., vol. Hi., 1900.
2 Hofbauer, "Zur Physiologic des Puerperiums," Monatsschr. f. Geburt.
und Gynak., vol. v., 1897.
3 Henderson, " Observations on the Maternal Blood at Term and during
the Puerperium," Jour, of Obstet. and Gyncec., vol. i., 1902.
i
FlG. 134. — Parous exter-
nal os (human). (From
Williams' Obstetrics,
Appleton & Co.)
THE FEMALE GENERATIVE ORGANS 551
compared with about 8000 in a normal woman. It is stated
that there is a diminution in the number of red corpuscles during
the first days of the puerperium, a circumstance which is
commonly ascribed to the loss of blood at delivery and the
lochial discharge. It is also said that the amount of haemoglobin
is reduced, and that there is a relative increase in the quantity of
fibrin and serum. Experiments show, however, that there is no
appreciable shortening in the coagulation-time of the blood,
such as has been supposed to account for the thrombosis of the
sinuses.1
The pulse rate during the early days of the puerperium is
usually stated to be somewhat below the normal, but according
to Longridge such cases are unusual. Williams a says that the
pulse is slowest on the second or third day, after which it
becomes quicker, resuming its normal rate after about ten days.
The temperature is ordinarily normal during the puerperium,
the old idea that the commencement of milk secretion was
associated with a rise of temperature having apparently no
basis in fact, excepting in cases of infection.
Little attention has been paid to the changes which occur
during the puerperal period in animals. Strahl has shown 3 that
the Mammalia with so-called full placenta (commonly called
Deciduata) can be arranged under three groups according to
the process of puerperal involution of the uterus. In the first
group, to which Man and monkeys belong, the epithelium is absent
from the mucosa, and requires, therefore, to be re-formed in the
manner described above. In the second group the placenta is
spread out over the inside of the uterus as in ^ the first group,
but in addition to this the inside of the organ is covered by a
layer of epithelium. This arrangement is found in Carnivores.
In the Rodents we often meet with the third form ; here, towards
the end of gestation, not only is the womb covered with cell-
tissue, but this epithelium also runs from the firrbrise right
underneath the placenta, undermining it till it is finally only
adhering to the walls oi the uterus by a slender cord carrying
1 Longridge, loc. cit. 2 Williams (Whitridge), loc. cit.
3 Strahl. " The Process of Involution of the Mucous Membrane of the
Uterus of Tarsius spectrum after Parturition," Proc. Section of Sciences,
Koninklijke Akademie van Wetenschappen te Amsterdam, vol. vi., 1904.
552 THE PHYSIOLOGY OF REPRODUCTION
the vessels. It is evident, therefore, that the uteri of the second
and third groups will resume relatively quickly their non-
puerperal appearance. The principal changes that occur are
the reduction of the surface epithelium both by the casting off of
superfluous parts and by the changing of larger cells into smaller
ones, the advance of new epithelium to cover places that were
bare,1 and the reduction and consolidation of the connective
tissue. The latter process is effected by the cells becoming
more compact, as in the bitch, or by a reduction in the amount
of inter-cellular substance, as in the hedgehog.2 The puerperal
changes in Tarsius are said to resemble those of Rodents.3
Excepting in those animals which belong to the first group
mentioned the lochial discharge is either very slight or absent
altogether.
The changes which take place in connection with the forma-
tion of milk in animals are described in the next chapter.
1 Duval, "De la Regeneration de 1'Epitheliura des Corne uterine apres
la Parturition," C. R. de la Soc. de BioL, vol. ii., Series 9, 1890.
2 Strahl, "The Uterus of Erinaceus europceus after Parturition," Proc.
Sect. Sciences, Kon. Akad. Wet. Amsterdam, vol. viii., 1906.
3 For the puerperal changes in Tupaia see von Herwerden, loc. cit.
CHAPTER XIII
LACTATION
" Nunc femina quseque,
Cum peperit, dulci repletur lacte, quod omnis
Impetus in mammas convertitur ille alimenti."
— LUCRETIUS.
THE possession of mammary glands is an essentially mammalian
character. Their function is to provide nourishment for the
newly born young. They are present in both sexes, but are
usually functional in the female only. Their number and
position vary considerably in different species. There may be
only a single pair (Man), or as many as eleven pairs (Centetes).
The number in any particular species usually bears a relation to
the normal size of the litter, or to the requirements of the newly
born offspring. Thus in the guinea-pig, in which the young are
born in an advanced state of development, and can feed without
being suckled, there are only two mammary glands, while in
the rabbit, in which the newly born young are naked and help-
less and the gestation period is far shorter, there are seven or
eight mammae. In animals which possess a number of mammary
glands, these are usually arranged in two nearly parallel rows
along the ventral side of the thorax and abdomen. In other
cases they are restricted to the thorax (Primates, excepting
some lemurs, Cheiroptera, Sirenia, elephants, sloths) ; while
in others again they are confined to the inguinal region (Un-
gulates, Cetaceans).
In the cow and other Ungulates the mammae are contained
within a definite milk-bag or udder, which is surrounded by a
fibrous envelope and is suspended below the abdomen. The
udder is provided with milk cisterns or galactophorous sinuses
into which the ducts of the gland open and convey the milk
from the secretory acini. Each sinus communicates with the
exterior by a teat, there being four teats in a cow, corresponding
553
554 THE PHYSIOLOGY OF REPRODUCTION
to the four mammary glands (and sinuses) commonly called the
four " quarters." One quarter may run dry without the others.
There is a fibrous di ision consisting of yellow elastic tissue
between the two lateral halves of the cow's udder, but not
between the anterior and posterior parts. In the sheep there are
only two glands (lateral halves), sinuses, and teats (occasionally
four), and the mare is similar excepting that there may be two
or even four sinuses opening into one teat.
In Monotremes the mammary glands are stated to be
modified sweat glands, whereas in other mammalian orders
they are commonly regarded as representing sebaceous glands.1
In Monotremes alone there are no teats, the orifices of the glands
being mere scattered pores in the skin, the exuding milk prob-
ably passing along the hairs, which in this region are arranged in
bunches. In Echidna the orifices open into two depressions which
have been called the mammary pockets.2 Teats, which are
present in all other orders of Mammals, are of two kinds. In
one kind the skin in the region of the gland becomes raised up
in a circular rim, and in this way gives rise to a tubular teat or
nipple, into the base of which the ducts of the gland open. This
form of teat occurs in Carnivora and Ungulata. In the other
kind of teat the gland itself is raised into a papilla, as in Man
and other Primates, in Rodents and in Marsupials. The use of
the teats is to facilitate the process of sucking. In the Cetacea,
however, where the action of sucking is incompatible with the sub-
aqueous life of these animals, the ducts of the mammary glands
are enlarged into reservoirs (somewhat similar to the galacto-
phorous sinuses of Ungulates), from which the milk is ejected
into the mouths of the young by means of a compressor muscle.3
1 Brouha and certain other authorities regard the mammary glands in all
the Mammalia as modified sweat glands (" Recherches sur les Diverses Phases
du Developpement et de 1'Activite de la Mamelle," Arch, de BioL, vol. xxi.,
1905. This paper contains many references). Eggelung regards the mam-
mary glands either as homologous with sweat glands, or else as organs which
are sui generis being derived independently from the primitive merocrine
skin-gland (" Ueber den wicktiges Stadium in der Entwickelung der mensch-
lichen Milchdriise," Anat. Anz., vol. xxiv., 1904).
2 Wiedersheim, Comparative Anatomy of Vertebrates, Parker's transla-
tion, 2nd Edition, London, 1897.
3 Flower and Lydekker, An Introduction <o the Study of Mammals.
London, 1891.
LACTATION 555
In the male mammal, as just mentioned, the mammae do not
usually function, though milk is occasionally produced in Man at
birth and at puberty, and more rarely at other times. Male
goats and sheep have been known to yield milk exceptionally,
and the same is also said to be the case with male rats l (see
p. 584).
STRUCTURE OF THE MAMMARY GLANDS
The mammary glands are composed typically of a number
of lobes, which are themselves divisible into lobules. Each
lobule consists of connective tissue in which the convoluted
ducts of the gland are bound together. If these ducts are
traced backwards they are seen to arise from groups of secretory
alveoli. If they are traced forwards they are found to unite
together to form the lactiferous ducts, which in the human
subject are from fifteen to twenty in number, and open to the
exterior by minute apertures through the teat. The lactiferous
ducts at their point of origin from the lobular ducts are provided
with reservoirs in which the milk collects during the periods of
glandular activity (i.e. during lactation). These reservoirs in
some animals are of a very considerable size (e.g. whales, as
described above). The duct walls consist of areolar tissue
containing some unstriated muscle fibres. They are lined
internally by short columnar epithelial cells which become
flattened in the proximity of the nipple. A quantity of fat
generally covers the surface of the gland, excepting the nipple.
This fat is connected both with the skin in front and with the
glandular tissue behind. Like the latter it is lobulated by
processes of areolar tissue. The nipple also is formed of areolar
tissue with unstriated muscle fibres. It is richly supplied with
vessels which give it an erectile structure. The glandular
tissue also is plentifully supplied with vessels, which vary in
size according to the condition of the gland. The glands in
Man are innervated by branches from the anterior and lateral
intercostal cutaneous nerves. Sensitive papillae are present on
the surface of the nipple, and around it there is a small area of
skin, on which the ducts of little secretory glands open to the
exterior.
1 Wiedersheim, loc. cit.
556 THE PHYSIOLOGY OF REPRODUCTION
In the secretory cells of the lactating mammary gland an
active and a resting condition can be distinguished. In the
latter the lumina of the alveoli are wide, and the cells of the
lining epithelium form a single flat layer with centrally situated
nuclei. In the active condition the epithelial cells are long
and columnar, and project into the lumina, and some of them
have two nuclei.
In these cells numbers of granules and globules accumulate,
— '• ;' '•B^^S'w2<''afflr^'";''/>^^
--.,<... . .--,.,. .;_.•- :•.", ;,. ..,-::-, ;-..--> £'^>^-~
FIG. 135. — Section of mammary gland of woman. (From Schafer,
after de Sinety.)
a, lobule of gland ; 6, acini lined by cubical epithelium ; c, duct ;
t, connective tissue.
the former being probably of a protein nature, and the latter of
a fatty composition. Gradually the alveoli become charged
with a fluid containing detached cells and fatty globules. The
detached cells are usually filled with granules, staining with
osmic acid and seemingly identical with the colostrum corpuscles
which have been observed to occur in milk in the first few days
after parturition, and occasionally also at other times. These
colostrum corpuscles have been seen to exhibit amoeboid move-
ments, and so are probably leucocytes which have wandered
into the lumina of the alveoli.1 The secretory fluid also con-
1 Schafer, "The Mechanism of the Secretion of Milk," Text-book of
Physiology, vol. i., Edinburgh, 1898.
LACTATION
557
tains cells which are supposed to have been detached from the
epithelium, but, as will be seen presently, there is some doubt
regarding this point.
The alveoli secrete milk during lactation, not merely while
suckling is going on, but also at other times, so that milk tends
to collect in the ducts and especially in the reservoirs. It has
•%?& »(SiVf©7f ^%»
£"iv ->p;v ;^-*%^r^««?
'W^mi^w^ -.=... :«-.•>
;%-4^" ffi^jiv-ffi' •:
1ft
XiwSFt^
*>£&••••»• • '
^fi?3S34&
FIG. 136. — Section of mammary gland (human) during lactation
(highly magnified), a, acini ; b, duct.
been calculated that the udders of a cow could not contain the
quantity of milk which can be obtained from them at one milking,
so that in such cases at least it seems certain that the process
of secretion must be carried on during the time that the milk is
being drawn. Furthermore, the milk which is drawn latest
has been shown to have a different composition from that which
is first obtained, the proportion of solids to liquids undergoing
an increase as the process of milking is continued. This, how-
558 THE PHYSIOLOGY OF REPRODUCTION
ever, is believed to be due partly to the larger globules of fat
meeting with greater resistance in passing through the ducts
and so being retained until the end of milking. Lehmann l
has recorded an experiment in which a solution of sulphin-
digotate of sodium was injected into a vein of a goat which
FIG. 137.— Section of mammary gland (human) in full activity.
(From Schafer, after von Ebner.)
o, a', a", alveoli variously cut and distended by secretion ; g, g', com-
mencing ducts ; ?', connective tissue.
was immediately afterwards milked. By the time the udders
had been almost completely emptied, a blue tinge appeared in
the milk. After an interval of about an hour and a half the
animal was again milked, when it was found that the injected
sulphindigotate had penetrated in sufficient quantity to render
the milk quite blue.
Three different hypotheses have been put forward regarding
1 Lehmann, "Beitriige zur Physiologic der Milchbildung," Die land-
wirthschaftlichen Versuchs-Stationen, vol. xxxiii., 1887.
LACTATION 559
the manner in which the substances of which the milk is formed
pass out from the secretory cells. According to one view, the
cells themselves break loose and become disintegrated, setting
free their contents in the alveoli of the gland, just as in the case
of the sebaceous glands.
Another theory states that the cells simply excrete the
substances into the alveolar lumina without becoming detached
or destroyed themselves, as with the submaxillary mucous gland.
According to the third hypothesis the mammary gland in its
mode of activity occupies a position midway between the
FIG. 138. — Section through an alveolus with fat drops in cells. (From
Schafer, after von Ebner.)
e, cells of alveolus ; k, cells of basement membrane (m) ; i, connective tissue.
sebaceous and submaxillary glands ; some of the cells simply
discharging their contents into the lumina, while with others,
the central part of the cell, containing a degenerate daughter
nucleus, breaks away and becomes disintegrated, leaving the
basal portion still in position.
It has already been mentioned that the mammary glands of
all Mammals, with the exception of the Monotremes, are usually
regarded as being of the nature of modified sebaceous glands.
It was partly on account of this belief that certain of the older
writers held the view that the secretion of milk was the result
of a fatty degeneration leading to a complete disintegration of
the secretory cells of the mammary gland.1 According to this
1 Virchow, Die Cellular-Pathologie, Berlin, 1871.
560 THE PHYSIOLOGY OF REPRODUCTION
theory the colostrum corpuscles were the detached epithelial
cells. In opposition to this theory, it has been pointed out
that there is no evidence of the extensive cell multiplication,
such as would be required in order to supply the large number
of cells which, according to this hypothesis, would necessarily
become detached. Heidenhain * has shown that if this theory
is correct, the cells of the gland must be completely renewed as
often as five times in one day in order to provide the solid
constituents of the secretion.
The second of the above-mentioned theories receives con-
siderable support from the circumstance that it has the analogy
of the great majority of secretory glands.2 Moreover, the recent
investigation of Bertkau 3 points strongly to the conclusion that
any appearances of disintegration which the secretory cells
possess is due to imperfect fixation. This author states that he
found no necrobiosis of any kind in these cells, and he believes
that milk formation is a purely secretory process. The colostrum
corpuscles, according to those who hold this view, are of the
nature of wandering leucocytes.
The third theory was first suggested by Langer, and has
since been adopted, with various slight modifications, by
Heidenhain,4 Steinhaus,5 and Brouha6 and others. According
to their view the cells of the gland lengthen out, so that their
ends come to project freely into the lumina of the alveoli. The
projecting portions then undergo a process of disintegration
before or after becoming detached, and the cell substance passes
into solution to form the albuminous and carbohydrate constitu-
ents of the milk. The fat droplets which collect in the disintegrat-
ing part of the cell give rise to the milk fat. The basal portions of
the cell remain in position without being detached, and subse-
quently develop fresh processes, which in their turn become
1 Heidenhain, " Die Milchabsonderung," Hermann's Handbuch der Phy-
siologie, vol. iv., 1883.
2 Schafer, loc. cit.
3 Bertkau, " Ein Beitrag zur Anatomic und Physiologie der Milchdruse,"
Anat. Anz., vol. xxx., 1907.
4 Heidenhain, loc. cit.
5 Steinhaus, " Die Morphologic der Milchabsonderung," Arch. f. Anat.
u. Phye., Phys. Abth., Suppl., 1892.
6 Brouha's paper (loc. cit.) contains a full account of the literature.
LACTATION 561
disintegrated. It is believed, however, that some cells simply
discharge their fat droplets and other contents into the lumina,
while otherwise remaining intact.1
Steinhaus states that mitotic division of the cell nuclei in
the actively secreting mammary glands is of frequent occur-
rence, and that the daughter nuclei which lie in the outer portions
of the cells degenerate and share in the general process of dis-
sociation. Szabo 2 also records the occurrence of two or more
nuclei in the same cell during lactation, and similar evidence
of nuclear division has been observed by others. Moreover, it
is argued that this view is in no way inconsistent with the
generally accepted homology between the mammary and
sebaceous glands, since it is easy to understand how, in the
course of evolutionary development, the mode of secretion in the
glands in question might have undergone an alteration, whereby
the process of disintegration in the actively secreting cells
became gradually lessened as the character of the secretion
changed. On the other hand, if we suppose that the cells of
the mammary gland merely extrude their secreted materials
without undergoing any histological disintegration, it is more
difficult to uphold the homology in question. Lastly, it should
be mentioned that those who, like Steinhaus, support the theory
of partial disintegration, do not regard the colostrum corpuscles
as detached epithelial cells, as Heidenhain did, but agree with
those who uphold the purely secretory theory in supposing the
corpuscles to be of the nature of " mast cells/' or basophil
leucocytes which have wandered inward from the connective
tissue of the gland, as already described, and have made their
way into the lumina of the alveoli.3
1 Brouha, loc. cit. ; also " Les Phenomenes histologiques de la Secretion
lactee," Anat* Anz., vol. xxvii.
2 Szabo", " Die Milchdriise itn Ruhezustande und wahrend ihrer Thatig-
keit," Arch. f. Anat. u. Phys., anat. Abth., 1896.
3 For references to further literature upon the physiology of milk forma-
tion see Basch, "Die Physiologic der Milchabsonderung," Ergeb. des Phys.,
1903, Jahrg. See also the following for references to the histology : —
Bizzorzero and Ottolanghi, " Histologie der Milchdriise," Merkel and Bonnet's
Ergeb. d. Anat. u. Entwick., vol. ix., 1900, and von Ebner, "Von der Ge-
schlechtsorganen," Kdlliker's Handbuchder Gewebelehre des Menschen,vol. in.,
1902.
2N
562 THE PHYSIOLOGY OF REPRODUCTION
THE COMPOSITION AND PROPERTIES OF MILK
Milk is essentially an emulsion, its white appearance being
caused by the reflection of the innumerable fat globules which it
contains in suspension. These globules, which are from -0015
to -005 millimetres in diameter, tend to float chiefly at the top,
where they help to form the cream, or that part of the fluid
which is richest in fatty constituents. The specific gravity of
both human and cow's milk is from about 1-028 to 1-034.1 When
the cream is skimmed off the specific gravity of course rises.
It is not proposed in the present work to deal more than
very briefly with the composition and properties of milk in
different animals.2 Human milk and cow's milk have been
most fully investigated, and it will suffice in this place to give
a short account of their respective constituents.
The average composition of cow's milk as compared with
human milk is as follows : —
Cow's.
Human.
Water
. . . 88-3
3*0
88-8
ro
Fats .
3-5
35
Carbohydrates .
Salts .
4-5
07
6-5
0-2
100-0 100-0
The proteins of milk are caseinogen, lactalbumen, and lacto-
globulin. Of these caseinogen is the most important. This is
the substance which is acted on by the ferment of rennet, pro-
ducing the well-known clotting or curding of milk, when the
caseinogen is converted into whey albumen and insoluble casein.
Lactoglobulin and lactalbumen are only present in small
quantities.
The fats of milk, which occur in small globules as just de-
scribed, are olein, palmatin, and stearin, with small quantities
of butyrin, capronin, and other fats of lower composition.
Lecithin and cholesterin are also present in small amounts, at
1 Halliburton, " The Chemical Constituents of the Body and Food,"
Schafer's Text-book of Physiology, vol. i., Edinburgh, 1898.
2 See Halliburton, loc. cit., and Schafer.
LACTATION 563
any rate in cow's milk. The percentage of volatile fatty acids
is less in human than in cow's milk.
Lactose or milk-sugar is the carbohydrate of milk, but other
carbohydrates (animal gum, dextrin, &c.), have also been stated
to occur. Lactose under the influence of certain micro-organisms
becomes converted into lactic acid, which causes the souring of
milk.
Milk is rich in calcium and potassium salts (especially in
calcium phosphate), but magnesium, sodium, and other salts
(chiefly chlorides) are also present in small quantities. The
amount of iron in human milk is very slight, while in cow's
milk it is practically absent altogether.
Bunge l has pointed out that whereas the inorganic salts in
milk are present in different proportions from those found in
the blood plasma, these proportions are almost identical with
those occurring in the young animal. He supposes this similarity
to indicate an adaptation to the needs of the young. This point
is illustrated in the following table, which gives the respective
amounts of mineral constituents present in a hundred parts of
ash of (1) the young pup ; (2) dog's milk, and (3) dog's serum.
(1) Young (2) Dog's (3) Dog's
K2O .
Na2O .
CaO .
MgO . . .
Fe203 . . .
P-A •
01 . . .
Small quantities of oxygen, nitrogen, and carbon dioxide
gases have been found in solution both in human and in cow's
milk.
1 Bunge, Lehrbuch der Physiologische und Pathologische Chemie, Leipzig,
1887, and various original papers. Of. Abderhalden, " Die Beziehungen der
Wachsthumsgeschwindigkeit der Sauglinge zur Zusammensetzung der Milch,"
&c., Zeitschr.f. Phys. Chem., vol. xxvi,, 1899, and other papers by the same
author in the same journal (vols. xxvi. and xxvii.)- For further references
see Lusk, The Science of Nutrition, Philadelphia, 1906. It is stated also
that the rennin of the stomach is specifically adapted for the coagulation of
the casein produced by the female of the same race.
Pup.
Milk.
Serum.
8-5
10-7
2'4
8-2
6-1
52-1
35-8
34-4
2-1
1-6
1-5
0-5
0-34
0-14
0-12
39-8
37-5
5-9
7-3
12-4
47-6
564 THE PHYSIOLOGY OF REPRODUCTION
The chief difference in the composition of cow's milk as
compared with human milk is the relatively high percentage of
proteins, fats, and salts, and the correspondingly low percentage
of lactose present in cow's milk.
Colostrum is the milk which is secreted during the first two
or three days after parturition. It contains less caseinogen
than ordinary milk, but considerable quantities of albumen and
globulin enter into its composition. It coagulates on boiling.
The characteristic colostrum corpuscles have already been
described.
The mammary glands of newly born animals sometimes
secrete small quantities of what is popularly called " witches'
milk/' This secretion contains most of the constituents of
normal milk, but the solid substances are usually less in amount.
It has an alkaline reaction.1
THE INFLUENCE OF DIET AND OTHER FACTORS ON THE
COMPOSITION AND YIELD OF MILK
The composition of the milk in any one species is subject to
some amount of variation, which is due to various causes.
Thus, the differences in the composition of cow's milk are said
to depend on the following factors : (1) The breed, (2) The
advance in the period of lactation, (3) The season of the year,
(4) The length of the interval between the times of milking,
(5) The occurrence of sexual excitement, (6) Situation and
climate, (7) Meteorological changes, and (8) The character of
the food.2 These factors may now be briefly discussed.
1 For fuller information about the constituents and properties of milk,
with tables of composition for different animals, and numerous references to
the literature, see Halliburton, loc. cit. See also Raudnitz, " Bestandteile,
Eigenschaften und Veranderungen der Milch," Ergeb. der Phys., 1903,
Jahrg. 2, where certain later papers are referred to ; and Abderhalden, loc. cit.
2 Crowther, Milk Investigations at Garford, Leeds, 1904. Droop Rich-
mond, "The Composition of Milk," Analyst, vol. xxxi., 1906. Lander,
" The Variation in the Composition of Milk," Bulletin XL issued by the
Edinburgh and East of Scotland College of Agriculture, 190G. Crowther,
" The Chemical Composition of Butter," Trans. Highland andAgric. Soc., vol.
xix., 1907. Gilchrist and Jones, " Dairy Investigations in the North-East
of England," Trans. Highland and Agric. Soc., vol. xviii., 1906, and vol.
xix., 1907.
LACTATION 565
That the yield and composition of the milk varies in the
different breeds is generally admitted. Thus Jersey cows yield
a larger proportion of butter fat than Ayrshires. But of all the
factors enumerated above, diet is perhaps the most important.
The richest and aLo the most abundant supply of milk is usually
yielded when the food supply is liberal. As a result of giving
food rich in protein substances, the milk supply tends to contain a
larger quantity of protein, sugar, and fat (especially the latter).
Schafer has pointed out, however, that because an excess of a
particular organic principle in the food causes an increase of
certain constituents in the milk, it must not be supposed that
these constituents are necessarily formed directly from such
material, " for the effect may be produced indirectly by the
functions of the gland-cells becoming modified, according to the
nature of the pabulum they are receiving. Looked at in this
light, certain substances may be said to stimulate the cells of
the glands to increased activity in all directions, tending to the
production of a larger quantity of milk rich in all kinds of sol d
constituents ; whilst other substances may be looked upon as
stimulating the cells in a special manner, tending to the increased
production of certain only of the constituents of the milk/' l
According to Crowther's researches on cows, change from a
highly nitrogenous diet to one relatively poor in nitrogen causes
secretion of a greater quantity of milk, but there is a decrease
in the fat content, this being more pronounced in the morning
than in the evening milk. A change in the reverse direction
effected an improvement in the quality of the milk. Concen-
trated food given either in the morning or evening tended to
increase the fat content of the morning milk, but had little or
no effect upon the evening milk. These alterations were found
to persist without appreciable diminution for fully five weeks
after the change of treatment.
There are a number of preparations in the market, known as
galactagogues, which are said to increase the flow of milk in
women, but, according to Williams, any virtue which they
possess is due largely to the quantity of fluid which is taken
1 Schafer, loc. cit. There is evidence also that an abnormal diet during
and previous to pregnancy may arrest the normal mammary development.
See Watson (B. P.), "The Effect of a Meat Diet on Fertility and Lactation,"
Proc. Roy. Soc. Edin., vol. xxvii., 1907.
566 THE PHYSIOLOGY OF REPRODUCTION
with them.1 It is stated also that certain particular foodstuffs
have a very appreciable effect upon the quantity and quality
of milk in cows. Thus bean-meal is said to increase the flow of
really good milk, unless it is given in immoderate quantities.
Brewers' and distillers' grains are likewise described as having
a beneficial influence upon the milk supply, but if given too
freely they tend to injure the breeding capacity, and in conse-
quence are most used in town dairies where the cows are
not bred from.2 Many substances ingested by the mother pass
unaltered into the milk. It is well known that certain foods
(e.g. turnips) cause an unpleasant taste or smell in the milk of
cows to which they are supplied. Lehmann's experiment, in
which sodium sulphindigotate was injected into the veins of a
goat, and shortly afterwards made its appearance in the milk,
has been already referred to (p. 558). So also it has been found
that immunity from disease may be acquired by young animals
being suckled by a female which had previously become immune,
the antibody to the disease being absorbed in the ingested milk.
It is generally recognised that the nature of the surroundings
has an influence over the mammary secretion. For example,
the composition of the fat in the milk of cows varies with the
condition of the animals. Circumstances tending to cause
discomfort usually lower the proportion of volatile acids present
in .the butter-fat, but the variation in the composition is very
irregular, and appears to depend partly upon the nervous
temperament of the cow. Extremes of heat and cold are said
to produce a decrease in the percentage of volatile acids, a fact
which has been put forward as an explanation of the general
poorness in these compounds of butters from Siberia and
other cold climates. Unseasonable and inclement weather is
believed to have a similar influence.3
In women exercise in the open air may not infrequently
increase the flow of milk. Nervous and mental influences or
any cause which affects the general metabolism may so change the
character of the secretion in women as to make it no longer fit
1 Williams, Obstetrics, London, 1904.
2 Wallace (R.), Farm Live Stock of Great Britain, 4th Edition, Edinburgh,
1907.
3 Crowther, loc. cit.
LACTATION 507
for the child. Violent emotion or shock have been known to
lead to the complete suppression of the mammary secretion.1
The employment of certain drugs also influences it. Thus
atropine, if given in sufficient quantities, stops the secretion
altogether, or if supplied in smaller amounts causes the milk to
become more concentrated.
The occurrence of menstruation in women, or of heat in
certain animals, may have a deleterious influence upon the milk,
and so upon the offspring (see p. 334). In the case of cows,
oestrus generally has a marked effect on the milk-yield, which as
a rule shows at first a perceptible diminution, followed usually
at the next milking by a yield well above the average. The fat
content is generally at first considerably reduced, but at the
following milking is sometimes abnormally high, or may be still
abnormally low. On the two or three days preceding the
outward manifestations of heat, the fat content tends to be
decidedly above the average.
Castration is stated to have a beneficial effect upon goat's
milk, relieving it of the characteristic hircine odour, increasing
the quantity of butter, casein, and phosphoric acid (though
decreasing the lactose present), and producing a greater and
more long-continued secretion.2 The removal of the ovaries
in cows may also tend to improve the quality of the milk,
rendering it richer than when the animals have been some
months pregnant.3
The advance of lactation may be accompanied by changes
both in the amount and in the composition of the mammary
secretion, but the changes vary greatly in different individuals.
In cows, the milk fat secreted in the first few days after parturi-
tion is poor in volatile acids, but it tends to improve rapidly
during 'the first few months, the improvement being maintained
until near the close of the lactation period, i.e. in most cases
near the approach of the next parturition.4
1 Williams, loc. cit.
2 Oceanu and Babes, " Les Effets Physiologiques de I'Ovariotomie,"
C. R. de VAcad. des Sciences, vol. cxl., 1905.
3 Wallace, loc. cit.
4 In cows which are " drying off," the percentage of volatile acids in
the butter fat is very low. See Crowther, loc. cit.
568 THE PHYSIOLOGY OF REPRODUCTION
THE DURATION OF LACTATION
The duration of the lactation or nursing period in the
different species of animals is governed mainly by the needs of
the young. In such animals as the guinea-pig, in which the
young are born in a sufficiently advanced state of development
that they are able to fend for themselves, the length of the lacta-
tion period is relatively short and inconstant, while hi other
animals, belonging to the same order of Mammals, the young are
born helpless, and are dependent for some weeks upon their
mother 's milk. In the larger animals the period of nursing is
of course longer, but in them also its average duration appears
to depend largely upon the necessities of the offspring.
The natural period of lactation in the cow is between nine
and ten months, allowing for an interval of from two to three
months to prepare for the next milking period. The duration
of the period in any given animal depends to some extent upon
such factors as diet and general treatment as described above,
but there is much individual variation. Some cows continue
to give milk until the next calving, but without a rest they are
liable to yield a less abundant supply in the succeeding year.1
It follows that a new gestation period in the cow has no
arresting influence over the mammary secretion. Cows which
have been castrated during lactation may yield milk for years
without any cessation, and thus give on the aggregate a larger
supply than cows which calve annually in the ordinary way.
It is well known that constant milking acts as a stimulus to
the secretory activity, and that cows which are not milked
soon " run dry/'
In the human female a year may be regarded as the -normal
period of nursing, any longer time involving what is known as
hyperlactation. The practice of hyperlactation is said to be
common, but it is to be deprecated in the interests of the infant.2
It would appear that if continuous suckling is encouraged, the
1 Wallace, loc. cit.
2 Dingwall Fordyce, "An Investigation into the Complications and
Disabilities of Prolonged Lactation," &c., an extension of papers published
in the Lancet, the British Medical Journal, and the British Journal of
Children's Diseases, 1906.
LACTATION 569
supply of milk in strong, healthy women may last almost inde-
finitely. As already mentioned, menstruation not infrequently
commences to recur during the lactation period, and the latter
may overlap gestation until within a short time of delivery.
THE DISCHARGE OP MILK
The ^'discharge of the milk from the lactiferous ducts which
occurs during sucking is due partly to the direct mechanical
pressure, and partly to the action of the muscular tissue which
is present in the walls of the ducts and in the nipple. The
muscular mechanism appears to be stimulated reflexly by the
action of sucking. The contraction of the muscles in the nipple
causes this structure to stiffen, and it is suggested that this
action has the effect of keeping open the orifices of the ducts,
and thus permitting the free outflow of milk.1
It is probable also that the discharge of the secretion is
assisted in some degree by the swelling of the entire mammary
gland resulting from a reflex dilatation of the vessels ; but if
the secretory process is very active, and the ducts are heavily
charged, the flow of milk may take place almost automatically,
and with hardly any external stimulus.
THE FORMATION OF THE ORGANIC CONSTITUENTS OF MILK
The principal organic constituents of milk are peculiar to the
secretion, a fact which shows that they are elaborated in the
mammary glands themselves, and not elsewhere in the body.
It is stated, however, that a relatively small amount of caseinogen
is present in the secretion of the sebaceous glands, from which,
as already remarked, it is commonly supposed that the mammary
glands 2 have been derived in the course of evolution. Nothing
appears to be definitely known regarding the method of forma-
tion of the caseinogen of milk,3 but it has been suggested that it
is derived from the degenerate nuclei of the gland cells.
1 Schafer, loc. cit.
2 Neumeister, Lehrbuch der physiologischen Chemie, vol. ii., Jena, 1895.
3 Thierfelder, " Zur Physiologie der Milchbildung," Pfluger's Archiv,
vol. xxxii., 1883.
570 THE PHYSIOLOGY OF REPRODUCTION
The precise method by which the milk fat is formed is like-
wise unknown. It may be derived from protein material, the
change being effected in the cells of the gland, or some of it may
possibly have its source in fat which has already been formed
elsewhere, and carried to the mammary glands in the blood or
lymph. There is no reason for supposing that the cells of the
glands do not possess, in common with most other tissues, the
power to elaborate fat. On the other hand, there is definite his-
tological evidence that they have this capacity (see above, p. 560).
Moreover, the special composition of the milk fat seems to be
by itself conclusive evidence that it is constructed within the
mammary glands.
The suggestion has been made that the leucocytes which
migrate through the epithelium and make their way into the
secretory fluid may help to bring fatty globules into it,1 but
there seems no necessity for assuming that this is the case.
The fat formation which takes place in the cells of the lacteal
glands in the process of milk manufacture has been compared
with the fatty degeneration which occurs in other tissues, milk
being nothing more than an emulsion of the fat of butter in
a solution of salts, proteins, and sugar. " What occurs as a
normal process in the cells of the lacteal glands occurs under
pathological conditions in much greater extent in very various
tissues, and leads almost always to incurable and fatal losses,
since as a rule no reparation is made by the younger cells/' 2
" The production of milk/' says Virchow,3 " in the brain instead
of in the lacteal glands, constitutes a form of brain softening.
The same process that in the one place affords the happiest
and sweetest results, in another induces a painful and bitter
wound." It has already been mentioned, however, that the
fat of milk has a special composition of its own, so that too
much stress must not be laid upon a resemblance between the
secretion of milk and the pathological formation of other fluid
substances in different parts of the body.
The mode of formation of the sugar of milk has been the
1 Michaelis, " Beitrage zur Kenntniss der Milchsecretion," Arch. f.
Mikr. Anat., vol. xxi., 1898.
2 Verworn, General Physiology, Lee's Translation from the second German
edition, London, 1899. 3 Virchow, loc. cit.
LACTATION 571
subject of some controversy. Bert l supposed that it was formed
from glucose which was absorbed by the cells of the mammary
gland from the circulating blood. The glucose, according to
this view, was manufactured in the liver, or, at any rate, elsewhere
than in the mammary gland. Bert based his hypothesis upoiT
two experiments in which the glands were removed from goats
which afterwards became pregnant. The urine of each animal
was tested during pregnancy to see if any reducing agent was
present, but no such substance could be found prior to the
birth of the kid. On the other hand, for several days after
parturition a substance which reduced cupric sulphate was dis-
covered in each case. Bert concluded that this was glucose.
He supposed further that the reducing body present in the
urine of the two goats represented glucose which in normal
animals would have been converted into lactose in the mammary
glands. The experiments were afterwards repeated by Moore
and Parker,2 who operated likewise upon two goats, and obtained
results which were the direct opposite of those of Bert. These
authors consequently concluded that the complete process of
lactose formation takes place in the cells of the mammary glands.
The question was subsequently reopened by Porcher,3 who
also repeated Bert's original experiment on a goat. After par-
turition in the operated animal, an intense glycosuria is said
to have occurred, the phenylhydrazine test showing that the
substance present in the urine was glucose, and not lactose or
some other reducing body. Porcher also removed the mammary
glands from four goats and one cow during lactation, and for a
few hours after the operation obtained marked glycosuria. As
a result of those experiments, taken in conjunction with those
of Bert, he concluded that the truth of the latter 's theory was
established beyond all doubt.
More recently the writer, working in conjunction with Dr.
1 Bert, " Sur 1'Origine du Sucre du Lait," C. R. de VAcad. des Sciences,
vol. Ixxxviii., 1884.
2 Moore and Parker, " A Study of the Effects of Complete Removal of
the Mammary Glands in Relationship to Lactose Formation," Amer. Jour.
of.Phys., vol. iv., 1900.
3 Porcher, "Sur 1'Origine du Lactose," C. R. de VAcad. des Sciences,
vol. cxxxviii., 1904. "De la Lactosurie," Monographies Cliniques, Paris,
1906.
572 THE PHYSIOLOGY OF REPRODUCTION
Kirkness,1 carried out a series of experiments upon guinea-pigs.
The mammary glands were removed prior to pregnancy (four
cases) or during pregnancy (one case). The urine was tested
for sugar both before and after parturition, but none was found
in any of the experiments. Other experiments showed that
glycosuria may occur after parturition in normal unoperated
animals, but that it does not do so invariably.2 When glycos-
uria does so take place, its occurrence is probably comparable
to post-operative glycosuria, the cause of which is not under-
stood. The glycosuria observed by Porcher after the removal
of the mammary glands during lactation may perhaps be
explained as an ordinary post-operative effect, and cannot be
cited as proof of Bert's hypothesis.
According to Thierfelder 3 and Landwehr,4 a formation of
lactose may take place if pieces of fresh mammary tissue are
kept in normal salt solution at body temperature. The lactose
is said to be formed from a precursor which Landwehr identified
as " animal gum " or carbohydrate of low reducing power.
According to Foa, there is a diminution of glucose in the
venous blood coming from the mammary glands, but the amount
of glucose and other carbohydrates present in the blood during
lactation is no greater than in normal blood.5
Muntz 6 has put forward the view that the lactose of
the mammary secretion is formed by the union of glucose,
the normal sugar of the organism, with galactose, which is
1 Marshall and Kirkness, " On the Formation of Lactose," Biochem. Jour.,
vol. ii., 1906.
2 Puerperal glycosuria and lactosuria have been described in women in
a number of cases. Lactosuria is also stated to occur not infrequently in the
late stages of pregnancy both in women and animals, the lactose in such cases
being presumably derived from the mammary glands by a process of absorp-
tion. See Hofmeister, " Ueber Laktosurie," Zeitsch.f. Phys. Chemie, vol. i.,
1877; Porcher, De la Lactosurie, 1906; and "L'Origine du Lactose," Arch.
Internat. de Phys., vol. viii., 1909. See also p. 510.
3 Thierfelder, "Zur Physiologic der Milchbildung," Pfluger's Archiv.
vol. xxxii., 1883.
4 Landwehr, "Ueber die Bedeutung des tierischen Gummis," PJiiiger's
Archiv, vol. xl., 1887.
6 Foa, " Sull' Origine del Lattosio del Latte," Arch, die Fis., vol. v., 1908.
6 Muntz, "Sur 1' Existence des Elements du Sucre de Lait dans les
Plantes," Annales de Chim. et de Phys., vol. x.
LACTATION 573
supposed to be derived directly by hydrolysis from certain
polysaccharide substances introduced in the food. It is pointed
out further, that such substances are present in plants which
form the normal diet of certain animals. It would appear,
however, that there is no direct evidence that lactose is actually
formed in this way. Moreover, this theory can scarcely be
applied to carnivorous animals, as Porcher 1 has pointed out.
There is, therefore, but little evidence that lactose is ela-
borated in the mammary glands from any closely related carbo-
hydrate precursor carried thither from elsewhere in the body.
It is of course obvious that this sugar must be derived ultimately
from compounds contained in the food, and it would seem not
improbable that it is manufactured partly from protein sub-
stances, and not merely from other carbohydrates.
THE NORMAL GROWTH OF THE MAMMARY GLANDS
The growth of the mammary glands in the rabbit has been
described by Miss Lane-Claypon and Starling, from whose paper
the following account is taken.2
In the virgin animal of about eight to twelve months old
mammary tissue cannot ordinarily be detected with the naked
eye, but in stained preparations of the connective tissue sur-
rounding the nipple, it is possible to see the ducts which com-
prise the gland. These are generally restricted to an area of
not more than one centimetre broad. Sections show that the
gland at this stage consists entirely of ducts which are lined
with a single layer of flattened epithelium, and end blindly.
No traces of alveoli are to be seen in the gland.
By the fifth day after conception a marked change has taken
place in the gland, which now appears, on reflecting the skin
from the abdomen, as a clearly differentiated pink area, circular
in shape, and surrounding the position of each nipple. The
diameter of this area is from about two to three centimetres.
1 Porcher, " Sur la Physiologie de la Mamelle," Jour, de Med. Vet. de
I'ficole de Lyon, Sept. 30, 1905.
2 Lane-Claypon and Starling, "An Experimental Inquiry into the Factors
which Determine the Growth and Activity of the Mammary Glands," Proc.
Roy. Soc., B.t vol. Ixxvii., 1906. See also Brouha, loc. cit.
574 THE PHYSIOLOGY OF REPRODUCTION
Sections through the gland show that it still consists entirely of
ducts, but that these are in a state of active proliferation. The
epithelial lining no longer consists of a single cellular layer, but
is two or three cells deep, while the individual cells are more
swollen than those of the virgin gland, and mitotic figures are
commonly seen.
The mammary gland now grows rapidly, so that on about
FIG. 139. — Section of developing mammary gland of horse. (From
S chafer, after Hamburger.)
s, sebaceous glands ; v, blood-vessels.
the ninth day after conception, on reflecting the skin from the
abdomen, the entire surface is found to be covered with a layer
of glandular tissue, the margins of the individual glands being
practically contiguous, each of them having a diameter of from
five to eight centimetres. Sections show that the formation of
alveoli (i.e. definite secretory structures) has begun at this
period, especially at the periphery, where the gland is generally
somewhat thicker than in other parts.
From this stage onwards the growth of the ducts and the
LACTATION
575
formation of alveoli proceed rapidly, so that by the twenty-
fifth day of pregnancy the whole surface of the abdomen has
become covered by mammary gland tissue, which may be half
a centimetre thick. This tissue is seen in sections to consist^
for the most part of alveoli, in the cells of which fat globules
are in process of formation.
From about the ninth day onwards to the twenty-fifth it
FIG. 140. — Section of mammary gland (human) showing developing alveoli.
(From Schafer, after von Ebner.)
6, connective tissue ; d, undeveloped alveoli ; d', partially developed
alveoli ; g, blood-vessel ; m, portion of duct.
is usually possible to squeeze a watery fluid from the nipples.
During the last days of pregnancy this fluid assumes the char-
acteristics of normal milk, so that by the time of parturition,
which occurs in the rabbit on the thirtieth day after conception,
the glands are full of milk.
The multiparous rabbit differs from the virgin in pos-
sessing ready-formed alveoli at the beginning of pregnancy.
576 THE PHYSIOLOGY OF REPRODUCTION
Consequently the amount of mammary growth during the
gestation period of the multiparous animal is relatively less.
The changes which take place in the human female and in
other animals during pregnancy are in a general way similar
to those occurring in the rabbit. In women after the second
month the breasts are said to offer a nodular sensation on palpa-
tion, this being due to the hypertrophy of the mammary alveoli.
The nipples also enlarge, and at the same time become more
erectile and pigmented, while the areola surmounting the nipple
becomes broader and pigmented also, in dark individuals being
often almost black. The hypertrophy of the sebaceous glands
in the areola results in the formation of the so-called glands of
Montgomery, which appear as small round elevations. As
already mentioned, during the later months of pregnancy the
thin yellowish fluid known as colostrum can generally be
expressed from the nipples.
The mammary glands are said to undergo growth at puberty,
and there can be no doubt that a slight hypertrophy generally
takes place in connection with each period of procestrum and
oestrus. These changes must be ascribed to ovarian influence,
which, as has already been shown, is probably responsible for the
changes which occur at such times in the other generative organs.
Professor J. P. Hill informs me that in certain Marsupials the
amount of mammary growth occurring at each ovulation period
is so marked as to render it difficult to distinguish such animals
from pregnant ones. Gellhorn l refers to a case of a woman
who had abnormal mammary glands with seven nipples in the
neighbourhood of the mons veneris, and who yielded milk at
each menstrual period. Other similar cases have been recorded.
This phenomenon is, of course, contrary to the more usual
tendency for menstruation to be in abeyance during lactation.
THE FACTORS WHICH ARE CONCERNED IN THE PROCESS
OP MAMMARY GROWTH
It has just been mentioned that the mammary glands in the
female begin to undergo enlargement at the period of puberty
in correlation with the increase in ovarian activity. In Man
i Gellhorn, "Abnormal Mammary Secretion," Jour. Amer. Med. Assoc.,
Nov. 21, 1908.
LACTATION 577
the difference between the glands in the two sexes is first mani-
fested at this time. The slight hypertrophy which occurs in
connection with each prooestrous period has been referred to,
while the great growth which the glands undergo during preg^_
nancy has also been described. It would appear, therefore,
that the stimulus to mammary growth, which arises originally
in the ovary, is afterwards derived from the developing embryo.
This view is supported by the fact, which has been established
experimentally, that mammary development succeeded by
lactation after parturition can occur in animals whose ovaries
have been extirpated at about mid-pregnancy or even at a
slightly earlier period.
It was formerly supposed that the connection between the
growth of the mammary glands and that of the embryo in the
uterus was a nervous one — that is to say, that the hypertrophy
of the glands was determined reflexly through the central nervous
system. There is now, however, abundant evidence that such
is not the case. This is shown, for example, by the experiment
performed by Goltz and Ewald,1 which has already been referred
to in considering the factors concerned in parturition. The
lumbo-sacral part of the spinal cord was completely exsected
in a pregnant bitch, so that all possible connection between
the mammary glands and pelvic organs through the nervous
system was destroyed. Pregnancy was accompanied as usual
by mammary development, and after parturition, lactation
occurred normally. Kouth's case,2 in which normal lactation
took place in a woman with complete paraplegia below the
level of the sixth dorsal vertebra, has also been referred to
(p. 538). Moreover, it has been shown by Eckhard 3 that after
complete severance of the nerves (branches of the external sper-
matic) passing to the mammary gland, the activity of the latter,
and consequently the supply of milk, are in no way affected.4
1 See pages 490 and 538.
2 Routh, " Parturition during Paraplegia, with Cases," Trans. Obstet. Soc.
vol. xxxix., 1897.
3 Eckhard, Beitrdge zur Anat. u. Phys., vol. i., Giessen, 1855.
4 Eckhard's experiments have been repeated by others with somewhat
contradictory results (see Basch, loc. cit.} ; Rb'hrig (" Experimentelle Unter-
suchungen iiber die Physiologie der Milchabsonderung," Virchow's Archiv,
vol. Ixvii., 1876) found that the external spermatic nerve contained-
2o
578 THE PHYSIOLOGY OF REPRODUCTION
Further evidence in support of the conclusion that the con-
nection between mammary and foetal growth is not nervous in
character is supplied by those experiments in which portions of
gland were successfully transplanted to abnormal positions in
the body. Thus in an experiment on a guinea-pig Ribbert x
grafted mammary tissue from the normal position to the neigh-
bourhood of one of the ears. Notwithstanding the fact that
the transplanted gland had lost its normal nervous connections,
it underwent enlargement during a subsequent pregnancy, and
afterwards secreted milk. Poster 2 states that he performed
a similar experiment on a rabbit, and obtained a similar result.
The inference is, therefore, that the relation between the
growth of the mammary glands and the development of the
foetus in the uterus is chemical in nature.
As Miss Lane-Claypon and Starling have pointed out, the
phenomenon of fertilisation succeeded by fcetal growth involves
the occurrence of changes in the ovaries and in the uterus (both
in the muscle and in the mucous membrane), as well as the forma-
vasomotor fibres for the vessels of the mammary gland, and that these affected
its secretory activity by controlling the blood supply. Mironow (" De
1'Influence du Systeme Nerveux des Glandes Mammaires," Arch, des Sciences
Biol. de St. Petersbourg, vol. iii., 1894) states that artificial stimulation
causes a reduction in the quantity of secretion. He states further that
whereas section of the external spermatic on one side has no effect on the
secretion, section on both sides diminishes it, but that the diminution only
comes on gradually after a number of days. After complete severance
of all the nerves in pregnant animals the glands may continue to grow and
yield milk after parturition. Basch (loc. cit.) states that extirpation of
the caeliac ganglion or transection of the spermatic nerve does not inhibit
the secretory process, but increases the number of colostrum corpuscles.
There is abundant evidence of a general kind that the central nervous
system in some way exerts an influence on the mammary gland. Thus the
effects of nervous shock in altering or inhibiting milk secretion in women
are well known. Moreover, the occurrence of uterine contractions on putting
the child to the breast, and so stimulating the nipples, is evidence of a
nervous connection. It would seem probable, therefore, that though the
mammary gland is essentially an automatic organ, the connection of which with
the generative organs is through the vascular rather than the nervous system,
yet it is under the regulating control of the latter by means of secretory
or vasomotor fibres.
1 Kibbert, "Ueber Transplantation von Ovarium, Hoden und Mamma,"
Arch. f. Entwick.-Mechanik, vol. vii., 1898.
2 Pfister, " Ueber die reflektorischen Beziehungen zwischen Mammae und
Genitalia muliebria," Beitrage zur Oeb. und Gynak., vol. v., 1901.
LACTATION 579
tion of an organ of complicated structure — the placenta — the
function of which is to nourish the developing young. The
question arose, therefore, as to whether the foetus or either of the
above-mentioned organs was not the direct source of formation^
of a hormone or chemical excitant which, after circulating in the
blood stream, acted as a stimulus to mammary growth.
It has been shown that the ovaries of rats can be removed
at any time during the second half of pregnancy (or somewhat
earlier) without interfering with the course of foetal develop-
ment or mammary growth, and, moreover, that lactation may
take place normally after the ovaries have been thus extirpated.1
It is evident, therefore, that though the ovaries may represent
the original source of the stimulus necessary for mammary
hypertrophy, they are not essential for the continuance of the
process, and exercise no sort of control over the final stages
which precede the secretion of milk.2
Furthermore, it has been shown that the mammary glands
undergo normal development in cases of extra-uterine fcetation
in which the growth of the uterus is relatively small. This
observation clearly indicates that the source of the stimulus in
question is not to be sought in the hypertrophied uterus. A
consideration of these and other facts led Miss Lane-Claypon
and Starling to the conclusion that one or other of the products
of conception (i.e. either the foetus or placenta), or possibly both,
were the seats of origin of the specific chemical stimulus which
brought about mammary growth.
Halban 3 had already formed the opinion, chiefly on clinical
grounds, that the specific stimulus arose mainly in the chorionic
villi and placenta.
More recently Ancel and Bo: in have laid stress on the close
parallelism between the development and regression of the cor-
pora lutea and mammary glands respectively in the rabbit.
1 Marshall and Jolly, " Contributions," &c., Phil. Trans., #., vol. cxcviii.,
1905.
2 Cf. Foges, "Beitrage zu der Beziehung von Mamma und Genitale,"
Wien. Uin. Woch., 1908, No. 5. Griinbaum (Deut. med. Wochenachr.,
1907, No. 20) has shown that mammary secretion may also occur after
hysterectomy.
3 Halban, " Die innere Sekretion von Ovariurn und Placenta und ihre
Bedeutung fur die Function der Milchdruse," Arch. /. Gynak.,\o\. Ixxv., 1905.
580 THE PHYSIOLOGY OF REPRODUCTION
This parallelism is said to exist even in the absence of
pregnancy.1
Miss Lane-Claypon and Starling appear to have been the first
to deal with the problem experimentally. In an initial series
of experiments they injected extracts or emulsions of ovaries
obtained from pregnant rabbits into other rabbits either sub-
cutaneously or intraperitoneally. In two further series of
experiments rabbits were injected with uterine and placental
emulsions or extracts. In no case, however, did the injections
produce any effect on the mammary glands, although in certain
of the experiments in which ovarian or uterine substance was
employed, marked swelling and congestion of the uterus were
afterwards observed.
The effect of injecting foetal extract was next tried, and this
led to definite positive results. When repeatedly injected into
female rabbits the extract was found to produce a genuine
development of the mammary glands which simulated the
normal growth which occurs during pregnancy. In one case a
virgin rabbit received fifteen injections of extract made from
many embryos of the same species. The injections were spread
over a fortnight, at the end of which the rabbit was killed. It
was found that a secretory fluid could be expressed from the
nipples, and that on reflecting the abdominal skin all the
mammary glands had grown to the size which is ordinarily
reached in a rabbit about eight days pregnant. In another
rabbit which received twenty-four injections, spread over five
and a half weeks, the effects produced were still more marked.
Further experiments showed that boiled extract was as effective
as unboiled, and the conclusion is therefore drawn that in all
probability the specific secretion or hormone is capable of with-
standing boiling. It was shown also that the substance in
question could be obtained equally well from different parts of
the foetus, that it passes through a Berkefeld filter, and that it
is not retained to any appreciable extent by the kieselgur in
Buchner's method for extracting cell juices.
Foa, states that extract of ox foetus, when injected into rabbits,
produced development of the mammary glands. He concludes,
therefore, that the stimulating substance which ciuses mammary
1 See page 343.
LACTATION 581
growth is not specific — i.e. not peculiar to any one kind of
mammal. Foa, says also that if the extract is heated to 110°
the active substance is destroyed, and no result is produced by
injection.1
THE FACTORS WHICH ARE CONCERNED IN THE COMMENCE-
MENT OP MAMMARY SECRETION
Since the growth of the mammary glands was apparently due
to a specific chemical stimulus arising in the foetus, it was natural
to suppose that the beginning of the actual secretory process
which marks the cessation of growth was caused by the removal
of this stimulus — in other words, by the expulsion of the foetus.
In this connection it is interesting to note that abortion or
premature labour is often followed by the appearance of milk
in the breasts.
The idea that lactation is due to the removal of an inhibition
appears to have been entertained first by Hildebrandt,2 who put
forward the suggestion that the developing embryo exerts an
influence whereby the cells of the mammary gland are protected
from those autolytic disintegrative processes which are supposed
to occur during active secretion. That the act of secretion is
to be ascribed to autolytic processes of the gland, is, according
to Miss Lane-Clay pon and Starling, highly improbable, and
there is no evidence that the autolysis of the gland cells would
give rise to the specific constituents which characterise milk.
Halban 3 has put forward the view that the specific stimulus
for mammary development arises in the placenta, while the
active secretion of the mammary glands is determined by the
expulsion or death of the placenta.4 Keiffer,5 on the other
hand, has entertained the contrary conception, that the secretion
of milk is due to a ferment elaborated in the placenta and trans-
1 Foh,, " Sui Fattori che determinano 1'Accrescimento e la Funzione della
Ghiandola Mammaria," Arch, di Fis., vol. v., 1908.
2 Hildebrandt, "Die Lehre von der Milchbildung," Hofmeistir's Bcitra-je,
vol. v., 1904.
3 Halban, loc. cit.
4 He points out that in cases of abortion the secretion of milk may not
begin until some days after the death of the child. This he believes to be
due to the circumstance that the placenta remained alive during the interval.
5 Keiffer, " Recherches sur 1' Anatomic et la Physiologic de la Mamelle,"
Bull, de la Soc. Beige de Gyn. et d'Obstet., 1901-2.
582 THE PHYSIOLOGY OF REPRODUCTION
f erred to the maternal circulation at the time of birth. These
theories are based mainly on clinical evidence of a somewhat
questionable value.
Miss Lane-Claypon and Starling have shown that after multi-
parous rabbits are injected with foetal extract milk is secreted by
the glands. This result is explained as follows : " The multi-
parous rabbit differs from a virgin rabbit in possessing ready-
formed alveoli, i.e. secretory structures. On the theory which we
have adopted, the circulation of the mammary hormone should
diminish any secretion in these alveoli, and should cause growth.
In all our experiments at least twenty-four hours elapsed between
each two injections. It is probable that the hormone was rapidly
absorbed from the injection, and was therefore present in the
blood of the animal only for a certain fraction, say a few hours,
out of the twenty-four. While it was circulating it should
cause building up of the secreting cells. Directly, however, it
ceased to circulate, the cells would enter into dissimulative
activity resulting in secretion. By our injections, therefore, we
are not able to imitate the continuous stimulus of pregnancy.
We are rather producing each day a pregnancy of a few hours
followed by a parturition. These factors should therefore
result in the production of milk in any animals possessing the
structures (i.e. the alveoli) which are capable of secreting
milk, and would therefore account for the secretion of milk
observed by us in all the cases where multiparous rabbits were
the objects of our experiment."
It has been shown that in the foetus itself there is an
increased growth of the mammary glands during the last part of
pregnancy, while it is well known that a secretion is often formed
in the glands of the newly born. Halban has explained this
secretion as the result of removal of the inhibitory influence —
that is to say, it is due to the same circumstance as the secretion
in the mother. Miss Lane-Claypon and Starling point out that
the complete change which occurs in the environment of the
newly born animal must induce equally profound changes in the
metabolism, and there is consequently no difficulty about the
conclusion that the formation of the mammary hormone ceases
with the commencement of extra-uterine life.
The general conclusions reached by these authors may be
LACTATION 583
summarised as follows : The anabolic changes associated with
the growth of the mammary glands are due to the assimilatory
effects of a hormone elaborated in the foetus and carried
thence through the placenta by the foetal and maternal circula-
tion. The removal of this stimulus produces those katabolicT
changes which are involved in the breaking down of the built-up
tissues and the consequent formation of milk.1
CRITICISMS
There are certain objections to be urged against these con-
clusions, which, however, are not claimed by the authors to be
as yet firmly established. Thus in certain animals the period
of lactation .may continue for an almost indefinitely long time, so
that it would appear as if the katabolic processes involved in
milk-secretion were out of all proportion to the anabolic pro-
cesses concerned in the building up of the gland tissue. For
example, it is stated that in castrated cows the mammary glands
may remain perpetually active for years and years so long as
milking is regularly continued (see p. 568). Moreover, in some
animals (e.g. mares) a secretion of milk may be induced artificially
as a result of a mechanical stimulus set up by repeated attempts
at milking. In one instance known to the writer, a mare which
had never had a foal could be made to yield milk at any time
for years. It would seem probable, however, that in such cases
there must have been an original tendency to secrete, and that
this tendency was merely augmented by the emptying of the
galactophorous ducts. This is in accordance with the view that
the emptying of the ducts during normal suckling constitutes a
physiological stimulus which acts on the gland cells, either
directly or by means of a reflex.
Heape 2 has pointed out as an objection to Starling's theory
of the foetal hormone that virgin bitches are frequently known to
produce milk, and that the quantity secreted may even be sufficient
to admit of their rearing pups. He also refers to a statement by
1 According to Foh, (loc. cit.) foetal extract has no inhibitory influence
on mammary secretion.
2 Heape, " The Source of the Stimulus which causes the Development of
the Mammary Gland and the Secretion of Milk," Proc. Phys. Soc., Jour, of
Phys., vol. xxxiv., 1906.
584 THE PHYSIOLOGY OF REPRODUCTION
Tegetmeier and Sutherland l that mules may yield milk in sufficient
abundance to rear a foal. He concludes, therefore, that the source
of the stimulus which excites the development of the mammary
glands is to be sought in the ovary rather than in the foetus.
Instances have also been recorded by Knott 2 and others,
in which males have secreted milk, thus showing that mammary
development is not necessarily even a female function ; but
such cases are at all events exceedingly rare.3 Knott mentions
cases in which suckling occurred in a bull, a male goat, a wether,
and in men. He also cites instances of virgin girls who were
nurses secreting copious supplies of milk as a consequence of
allowing infants to suck their nipples ; and thus he supports
Heape's objection to the foetal hormone theory. Gellhorn 4 cites
similar cases, including one of a virgin monkey (Cercopithecus).
Another case is mentioned of a woman who suckled children un-
interruptedly for forty-seven years, and in her eighty-first year
had a moderate but regular supply of milk,5 thus showing that
mammary secretion may continue exceptionally for long after the
menopause, and presumably, therefore, in the absence of any sort
of stimulus from the generative organs. This observation further
supports the idea referred to above, that normal suckling acts
by itself as a physiological stimulus for mammary secretion.
A more forcible objection to the theory of the foetal hormone
is supplied by the Monotremata, which are the lowest order of
Mammalia. These animals are oviparous, the developing
embryo being contained in an egg, which does not enter into
any sort of connection with the uterine wall. Halban,6 however,
has made the suggestion, which is quoted by Miss Lane-Claypon
and Starling, that since the embryo goes on increasing in size
during its passage down the female generative tract, and since the
shell of the egg is porous, it is not impossible that substances may
diffuse outward from the embryo and be absorbed by the uterine
mucous membrane, and so be carried into the maternal circulation.
1 Tegetmeier and Sutherland, Horses, Asses, Zebras, Mules, and Mule
Breeding, London, 1895.
* Knott, "Abnormal Lactation," &c., American Medicine, vol. ii. (new
series, June), 1907. Cf. Wiedersheim (see p. 555).
3 The occasional occurrence of milk secretion in the newly born, both
males and females, is well known.
4 Gellhorn, loc. cit. 5 Knott, loc. cit. ° Halban, loc. cit.
LACTATION 585
Miss Lane-Claypon and Starling, however, do not contend
that the foetus is the sole source of the stimulus for mammary
development. On the other hand, they specially mention that
the growth of the mammary glands which occurs at puberty,
for instance, can only be attributed to ovarian influence, since
it does not take place if the ovaries have been previously re-
moved. It is not improbable, therefore, that an ovarian stimulus
is also responsible for initiating the growth of the glands in
Monotremes, while Hill's observations on certain Marsupials
afford a clear indication that such is the case in these animals
(see p. 576).
APPENDIX
Lombroso and Bolafno l have described an experiment in
which two female rats were grafted together so that their re-
spective circulatory systems were presumably united. Subse-
quently to their union they each became pregnant, but at
different times. They afterwards produced young, one pre-
maturely, and the other at full term. The mammary glands-
of each underwent the characteristic changes, but they occurred
independently and not synchronously. The authors cite this
result as evidence against the foetal hormone theory. Moreover,
as a result of this and another similar experiment, they conclude
that parturition is not induced by a chemical excitant circulating
in the blood (see p. 542).
On the other hand, in the case of the Bohemian pygopagous
twins, Rosa-Josepha, the mammary glands of both are de-
scribed as having been similarly and simultaneously affected by
the pregnancy of Rosa, who bore a healthy boy on April 17, 1910.
Milk was afterwards secreted by the breasts of Josepha as well
as of Rosa, although Josepha had never conceived.2
1 Lombroso and Bolaffio, "La Parabiosi e la Questions del Fattori che
determinano laFuz Funzione mammaria e 1'Insorgenza del travaglio di parto,"
Atti della Soc. Ital. di Obstet. e Gin., vol. xv., 1909.
2 British Med. Jour., Part II., May 28, 1910. The twins are described
as being united posteriorly by a common sacrum, but the iliac bones are
separate. There is a common anus, perineum, clitoris, and meatus urinarius,
but the labia majora are double. The urethra is single for an inch above the
meatus, but then it bifurcates. The ureters are normal. The desire to
micturate is said to be distinct, but not the desire to defalcate.
CHAPTER XIV
FERTILITY
" Nam multum harmonise veneris diferre videntur.
Atque alias alii complent magis ex aliisque,
Succipiunt alias pondus magis inque gravescunt.
Atque in eo refert quo victu vita colatur." — LUCRETIUS.
THE rate of propagation in any species of animal depends not
only upon the average number of young born in each litter, but
also upon the frequency of recurrence of the sexual season and
the duration of the reproductive period in the animal's life.
The frequency of recurrence of the sexual season — that is to say,
the cestrous cycle — in different species of Mammals has been
discussed at some length in an early chapter of this work. In
the present chapter it remains to consider a little more closely
some of the causes which control this periodicity and the factors
which affect fertility.
The duration of the reproductive period of an animal's existence
extends in most cases from a time when that animal has almost
reached its full size until the beginning of senescence, so that the
normal period of generative activity in the individuals of any
given species bears a definite relation to their average length of
life. In the male the sexual maturity is usually reached later than
in the female. Moreover, in the male there is no definite ending
of the reproductive period, since in Man, for example, the power
of producing spermatozoa continues in a gradually diminishing
degree even in extreme old age, whereas in the female, on the
other hand, the climacteric marks the cessation of generative
activity (see below, p. 672).
Broadly speaking, the average number of young produced
in a litter in any species of Mammal is inversely proportional
to the average size of the animals belonging to that species.
Thus, in most species of Ungulates twins are the exception
rather than the rule ; and there are seldom more than two young
produced at a time even in sheep and goats, which show a greater
degree of fertility than most Ungulates. The sow, however, is
586
FERTILITY 587
exceptional in having very large litters, as many as seventeen
young being sometimes born. On the other hand, in small
Mammals such as Rodents large litters are the rule ; the rat,
for example, being known occasionally to bear as many as sixteen
or even twenty young ; but the Cheiroptera, or bats, are remark-
able for their relative infertility, only one young one ordinarily
being produced at a time, although the common bat is no larger
than the mouse.
Generally speaking, only one young one is produced in those
animals in which the period of gestation exceeds six months.
The number of teats characteristic of the species also affords
an approximate indication of the average size of the litter.
" Among women, the birth of twins occurs once in about
eighty deliveries. Triplets, quadruplets, quintuplets, and even
higher figures, are occasionally observed ; they are very un-
common, and the rarity is progressive with the number. The
normal or ordinary rule in woman is to bear one child at a time ;
and the next most frequent condition is temporary or persistent
sterility — two points in which she signally differs from what
is generally believed [of animals]/' l Veit's statistics 2 for
13,000,000 births in Prussia showed that twins were produced
once in 89 cases, triplets once in 7910, and quadruplets only
once in 371,125 cases. There is some evidence also that the
frequency of occurrence of multiple pregnancy in women depends
upon the race or climate, and that it is commoner in cold than
in warm countries.3
Herbert Spencer 4 elaborated a theory whereby he explained
the relative degrees of fertility in the different races of men and
animals. According to this theory the power to sustain individual
life and the power to produce new individuals are inversely
proportional, a conclusion which is summarised in the generalisa-
tion that Individuation and Genesis vary inversely. When
there is an abundant food supply and a favourable environment,
1 Matthews Duncan, Fecundity, Fertility, Sterility, and Allied Topics,
Edinburgh, 1866.
2 Veit, "Beitrage zur geburtshulflichen Statistik," Monatsschr. f. Geb.,
vol. vi., 1855.
3 For further statistics and references see Williams, Obstetrics, New
York, 1904.
4 Spencer, Principles of Biology, revised edition, vol. ii., London, 1899.
588 THE PHYSIOLOGY OF REPRODUCTION
and the necessary expenditure of energy is relatively slight, the
cost of Individuation is much reduced, and the rate of Genesis
is correspondingly increased ; in other words, there is a high
degree of fertility. Spencer cited the Boers, the Kaffirs, and the
French Canadians as examples of fertile races in which the rate
of increase is associated with a nutrition that is greatly in excess
of the expenditure. Conversely, he concluded that a relative
increase of expenditure leaving a diminished surplus reduces
the degree of fertility, and in support of this statement adduced
evidence that bodily labour tends to make women less prolific,
since the reproductive age is said to be reached a year later
by women of the labouring class than by middle-class women.
Spencer applied his generalisation to animals as well as to
Man, and attempted to explain thereby the average contrast
between the fertility of birds and Mammals. " Comparing the
large with the large and the small with the small, we see that
creatures which continually go through the muscular exertion
of sustaining themselves in the air and propelling themselves
rapidly through it, are less prolific than creatures of equal weights
which go through the smaller exertion of moving about over
solid surfaces. Predatory birds have fewer young ones than
predatory Mammals of approximately the same sizes. If we
compare rooks with rats, or finches with mice, we find like
differences. And these differences are greater than at first
appears. For whereas among Mammals a mother is able,
unaided, to bear and suckle and rear half-way to maturity a
brood that probably weighs more in proportion than does the
brood of a bird ; a bird, or at least a bird that flies much, is
unable to do this. Both parents have to help ; and this indi-
cates that the margin for reproduction in each adult individual
is smaller/'
Spencer cites numerous instances from among both birds
and Mammals illustrating the effects of different degrees of
activity upon fertility. The hare and the rabbit, for example,
are closely allied species, " similar in their diet, but unlike in their
expenditures for locomotion. The relatively inert rabbit has
six young ones in a litter, and four litters a year ; while the
relatively active hare has but two to five in a litter. That is
not all. The rabbit begins to breed at six months old ; but a
FERTILITY 589
year elapses before the hare begins to breed. These two factors
compounded result in a difference of fertility far greater than
can be ascribed to unlikeness of the two creatures in size."
Furthermore, Spencer refers to the case of the bat, which
has been already mentioned as being abnormally unprolific in
proportion to its size. The relatively low rate of multiplication
is of course ascribed to a relatively high rate of expenditure
resulting from the habit of flying.
In a similar way Spencer explains such well-known facts as
that hens cease to lay when they begin to moult. " While they
are expending so much in producing new clothing, they have
nothing to expend for producing eggs."
There can be little doubt that Spencer's generalisation is
in the main true, but it is equally certain that it cannot be
applied indiscriminately to explain the relative degrees of fertility
in all animals, and consequently it must not be pressed too far.
Some of the more special factors which control fertility are
referred to below, and it is evident that many (though not all)
of these fall within the scope of Spencer's generalisation.
The rate of increase as distinguished from the rate of repro-
duction (in any given species) depends upon a large number of
factors, of which the rate of reproduction is only one.
EFFECT OF AGE
Matthews Duncan x has discussed at some length the varia-
tion which occurs in the fertility of women according to their
age. He adduces statistical evidence showing that the fertility
of the female population increases gradually from the commence-
ment of the child-bearing period of life until about the age of
thirty, and then it gradually declines. He shows also that the
fertility is much greater before the climax is reached (at thirty
years) than after it is passed. These conclusions, however, apply
merely to the actual productiveness (i.e. the number of births),
as opposed to the capability of bearing children, which Duncan
designates the fecundity. By eliminating from his calculations
all women not living in married life, Duncan arrives at the
following conclusions, which are based on statistics showing the
1 Duncan, loc. cit.
590 THE PHYSIOLOGY OF REPRODUCTION
productiveness of wives : 1 (1) " That the initial fecundity of
women gradually waxes to a climax, and then gradually wanes " ;
(2) " That initial fecundity is very high from twenty to thirty-
four years of age " ; and (3) " That the climax of initial fecundity
is probably about the age of twenty-five years." The fecundity
of the average individual woman may be described, therefore,
as forming a wave which, starting from sterility, rises somewhat
rapidly to its highest point, and then gradually falls again to
sterility.
There can be no doubt that animals as a general rule tend
to follow a similar law. A dog generally has fewer puppies in
its first litters than afterwards, while in its declining years there
is a diminution until sterility is reached once more. The same
is said to be the case with the bear, the elk, and other animals,2
but there are obviously many individual exceptions. Geyelin 3
gives the following table showing the fertility of the domestic
fowl at different ages : —
First year after hatching 15 to 20 ! Sixth year after hatching 50 to 60
Second „ „ . 100 ,,120 ! Seventh „ „ . 35 „ 40
Third „ „ . 120 „ 135 j Eighth
Fourth „ „ . 100 „ 115
Fifth 60 „ 80
Ninth 1 „ 10
Furthermore Minot4 observed that in guinea-pigs the size
of the litters increased with age during the first sixteen months
of their lives.
EFFECTS OF ENVIRONMENT AND NUTRITION
That the generative system in animals is peculiarly susceptible
to changed conditions of existence has been recognised from
early days. Thus Aristotle 5 commented on the increased
fertility of sheep in a favourable environment. In more recent
1 It is, of course, obvious that it is impossible to determine statistically
the real "fecundity" (using the term as defined by Duncan) in view
especially of the practice of volitional interference with conception (see
below, p. 621). 2 Duncan, loc. cit.
3 Geyelin, Poultry-Breeding in a Commercial Point of View, London,
1865.
4 Minot, " Senescence and Rejuvenation," Amer. Jour, of Phys., vol.
xii., 1891.
5 Aristotle, History of Animals, Bonn's Library, London.
FERTILITY 591
times Buffon,1 among others, remarked on the fact that domestic
animals breed oftener and produce larger litters of young than
wild animals belonging to the same species ; and Darwin, who
made the same observation, attributed the increased fertility
of the former to a long habituation to a regular and copious"
food supply without the labour of seeking for it. " It is notorious
how frequently cats and dogs breed, and how many young they
produce at birth. The wild rabbit is said to breed four times
yearly, and to produce each time at most six young ; the tame
rabbit breeds six or seven times yearly, producing each time
from four to eleven young. . . . The ferret, though so closely
confined, is more prolific than its supposed wild prototype [the
polecat]. The wild sow is remarkably prolific ; she often breeds
twice in the year, and bears from four to eight, and sometimes
even twelve, young ; but the domestic sow regularly breeds
twice a year, and would breed oftener if permitted ; and a sow
that produces less than eight at birth ' is worth little, and the
sooner she is fattened for the butcher the better/ The amount
of food affects the fertility of the same individual ; thus sheep
which on mountains never produce more than one lamb at birth,
when brought down to lowland pastures frequently bear twins.
The difference apparently is not due to the cold of the higher
land, for sheep and other domestic animals are said to be
extremely prolific in Lapland." 2
Darwin remarks that birds afford still better evidence of
increased fertility resulting from domestication. Thus, in its
natural state the female of Gallus banJciva, the wild representative
of the common fowl, lays only from six to ten eggs ; the wild
duck lays from five to ten eggs, as compared with eighty or a
hundred produced by the domestic duck in the course of the
year. Similarly, the turkey, the goose, and the pigeon are more
fertile in the domestic state, though this is not the case with
the pea-fowl. Among plants also there are countless instances
of increased fertility as a consequence of cultivation.3
1 Buffon, Histoire Naturelle, Paris, 1802.
2 Darwin, The Variation of Animals and Plants under Domestication,
Popular Edition, vol. ii., London, 1905.
3 Cf. also Spencer (loc. cit.), who discusses this question at some length
in connection with his generalisation that Individuation and Genesis vary
inversely. See above, p. 587.
592 THE PHYSIOLOGY OF REPRODUCTION
On the other hand, it is well known that wild animals, when
removed from their natural conditions and brought into captivity,
often become partly or completely sterile. Darwin discusses this
phenomenon at some length, and cites numerous cases from
different groups of animals and birds.
The Indian elephant, for example, seldom breeds in captivity,
although kept in a perfectly healthy condition and in its native
country. On the other hand, most members of the Suidse are
known to breed in menageries and zoological gardens, while
many Ruminants breed readily in climates widely different from
their own. Carnivorous animals breed somewhat less freely in
confinement, and show considerable variation in different places.
The Canidae tend to be more fertile than the Felida?, while the
members of the bear group breed less easily. Rodents as a
general rule fail to breed after being brought into captivity, but
there are several exceptions. Monkeys also when kept in con-
finement only rarely have young ones. Many of these animals,
however, although failing to conceive, are known to copulate
freely. This is especially the case with captive bears and monkeys,
in which the typical phenomena of prooestrum and oestrus occur.
It would seem probable that the sterility under these circum-
stances results from a failure to ovulate, due possibly to an
absence of ripe follicles in the ovaries.
Among birds, members of the hawk group very seldom
breed in captivity. The graminivorous birds show considerable
variation, some, like the canary, breeding freely in aviaries
(although it was some time before it became fully fertile), while
others, like the finches, only occasionally reproduce their kind
when kept in confinement. Gallinaceous birds, on the other hand,
show an unusual capacity to breed in captivity, and the same
is the case with pigeons, ducks, and geese. Certain kinds of
gulls also are known to breed readily when kept in open spaces
in zoological gardens.
As pointed out by Darwin, there is other evidence that
changed conditions of life may induce a disturbance of the
sexual functions. Thus when conception does occur under
confinement, the offspring are sometimes born dead or ill-formed,
or otherwise show signs of insufficiency of nourishment. The
mother's milk may fail, indicating an interference with those
FERTILITY 593
factors which control the mammary metabolism. Moreover, in
animals which are characterised by a periodic growth of the
secondary sexual characters, these sometimes fail to make their
appearance. The male linnet in captivity does not assume
its characteristic crimson breast, or the male bunting (Emberiza
passerina) the black colour on its head. Other birds, such as a
pyrrhula and an oriole, may acquire the appearance of the hen,
while a falcon (Falco albidus) has been observed to lose its adult
plumage.1 These facts seem to show that the generative meta-
bolism may be so altered by changed conditions of existence as to
induce not merely a state of sterility, but also an interference with
the secretory activity of the essential organs of reproduction.2
Darwin says : " We feel at first naturally inclined to attribute
[such results] to loss of health, or at least to loss of vigour ; but
this view can hardly be admitted when we reflect how healthy,
long-lived, and vigorous many animals are under captivity, such
as parrots, and hawks when used for hawking, chetahs when
used for hunting, and elephants. The reproductive organs
themselves are not diseased ; 3 and the diseases from which
animals in menageries usually perish are not those which in any
way affect their fertility. The failure of animals to breed under
confinement has been sometimes attributed exclusively to a
failure in their sexual instincts. This may occasionally come
into play, but there is no obvious reason why this instinct should
be especially liable to be affected with perfectly tamed animals,
except, indeed, indirectly through the reproductive system
itself being disturbed. Moreover, numerous cases have been
given of animals which couple freely under confinement, but
never conceive ; or, if they conceive and produce young, these
are fewer in number than is natural to the species. . . . Change of
climate cannot be the cause of the loss of fertility, for whilst
1 Darwin, loc. cit.
2 The relation between the gonads and the secondary sexual characters,
and the apparent dependence of the latter upon the secretory activity of
the former, are discussed in Chapter IX.
3 Few observations have been made upon the condition of the gonads
in animals in captivity, but Branca (" Recherches sur le Testicule et les Voies
spermatiques dans Lemuriens en captivite," Jour, de V Anat. et la Phys.,
vol. xl., 1904) states that in captive lemurs he could find no spermatozoa in
the testicles.
2p
594 THE PHYSIOLOGY OF REPRODUCTION
many animals imported into Europe from extremely different
climates breed freely, many others when confined in their
native land are sterile. Change of food cannot be the chief
cause ; for ostriches, ducks, and many other animals, which
must have undergone a great change in this respect, breed
freely. Carnivorous birds when confined are extremely sterile,
whilst most carnivorous Mammals, except plantigrades, are
moderately fertile. Nor can the amount of food be the cause ;
for a sufficient supply will certainly be given to valuable animals ;
and there is no reason to suppose that much more food would be
given to them than to our choice domestic productions which
retain their full fertility. Lastly, we may infer from the case
of the elephant, chetah, various hawks, and of many animals
which are allowed to lead an almost free life in their native
land, that want of exercise is not the sole cause/' Darwin
shows also that close confinement by itself does not necessarily
cause sterility, since such animals as the rabbit and ferret breed
freely in cramped hutches. The general conclusion reached is
that " any change in the habits of life, whatever these habits
may be, if great enough, tends to affect in an inexplicable manner
the powers of reproduction. The result depends more on the
constitution of the species than on the nature of the change ;
for certain whole groups are affected more than others ; but
exceptions always occur, for some species in the most fertile
groups -refuse to breed, and some in the most sterile groups
breed freely."
In support of these conclusions Darwin shows further that
domesticated animals also under new conditions occasionally
show signs of lessened fertility, and that animals such as the
canary, which now breed readily in a state of captivity, were
formerly often sterile.
Bles' observations,1 to which reference has already been
made (p. 20), seem to have a bearing on this question. This
observer, who has kept various kinds of Amphibia in captivity,
has shown that axolotls can only be induced to breed under
certain special environmental conditions. By feeding them
copiously in summer and allowing them to hibernate in winter,
1 Bles, "The Life-History of Xenopus Icevis" Trans. Roy. Soc.
Edinburgh, vol. xli., 1906.
FERTILITY 595
and then suddenly transferring them to an aquarium stocked
with growing plants and provided with running water, these
animals could be induced to spawn within a few days. (Cf. also
Annandale's observations referred to on p. 22.) Bles draws the-
conclusion that the difficulty so often experienced in inducing
Amphibians to breed in a state of captivity is not due to toxic
influence on the gonads resulting from the confinement, but
must rather be ascribed to the absence of the necessary external
stimuli without which the generative organs of animals are
incapable of properly discharging their functions. Bles suggests
that this view may help to explain why some animals (e.g. insects)
make their appearance in great numbers in one year, and are
comparatively scarce in another.
In animals which as a general rule breed freely in a state of
domestication or under confinement, it is probable that nutrition
plays the chief part (though by no means the sole part) in re-
gulating the capacity to produce offspring. That an insufficient
or markedly abnormal diet must affect this power is almost
self-evident, and Chalmers Watson 1 has shown that sterility is
a common condition among caged rats when fed exclusively
upon meat. It is also certain that an excessive quantity of
nutriment is likewise prejudicial to the proper discharge of the
reproductive functions. No better example could be given of
the way in which overfeeding results in a condition of sterility
than that of the barren Shire mares, which in recent years have
been a striking feature at agricultural shows in England. Some
foods are said to induce sterility more easily than others. Sugar,
molasses, and linseed are noted for having this effect when given
to cattle, but they are often used to prepare beasts for show
or sale, since they produce a good coat of hair and cause a
deposit of fat. Very fat animals do not come in season so often,
and consequently cattle " settle better and feed faster as they
become what the butchers designate ' fat ripe/ " l In such
animals there can be no doubt that the ovarian metabolism
is abnormal, for the author has often found large quantities
of bright orange-coloured lipochrome in the interstitial tissue
1 Campbell and Watson, «« The Minute Structure of the Uterus of the Rat,"
&c., Proc. Phys. Soc., Jour, of Phys., vol. xxxiv., 1906.
596 THE PHYSIOLOGY OF REPRODUCTION
of the ovaries of fat cows and heifers. A low condition,
especially if associated with exposure to wet and cold, as
in the case of cattle wintered in the open air, or of cows
which have suckled a large calf or more than one calf, is also
a common cause of temporary barrenness.1 Certain other
more special causes of sterility are referred to briefly below
(p. 606).
A few years ago the Royal Agricultural Society of England
instituted an inquiry into the subject of fertility in sheep. The
investigation was conducted by Heape, at whose instigation it
was carried out. In the report 2 which was subsequently pub-
lished a comparative account is given of the fertility of various
breeds of sheep chiefly in the south of England in the season 1899.
The most fertile breed was the Wensleydale, in which six flocks,
consisting of a total of 319 ewes, produced a percentage of
177*43 lambs. The effects of locality are discussed, and there is
an accumulation of evidence indicating that the character of
the district is not without influence on the fertility of the breed.
Thus, Lincoln sheep run on the wolds, Shropshire sheep on a
subsoil of new red sandstone, and Hampshire sheep, which are
not run upon chalk downs, are shown to be associated statistically
with a relatively high percentage of infertility. The report
shows further that the fertility of a flock depends greatly upon
its management, that the quality and quantity of the food
supplied affect the condition of the sheep, and so influence
their power to breed, that some seasons are more favourable to
fertility than others, and that sheep-stained pasture (or pasture
on which sheep have run for some considerable time previously)
is detrimental to breeding stock.
The present writer has shown3 that in Scotch Blackfaced,
Cheviot, and other Scottish sheep the normal percentage of ova
discharged at any single oestrous period is not appreciably in
excess of the usual percentage of births at the lambing season.
1 Wallace (R), Farm Live Stock of Great Britain, 4th Edition,
Edinburgh, 1907.
2 Heape, " Abortion, Barrenness, and Fertility in Sheep," Jour. Roy.
Agric. Soc., vol. x., 1899. See also Heape, "Note on the Fertility of
Different Breeds of Sheep," &c., Proc. Roy. Soc., vol. Ixiv., 1899.
3 Marshall, "The (Estrous Cycle and the Formation of the Corpus
Luteum in the Sheep," Phil. Trans., B., vol. cxcvi., 1903.
FERTILITY 597
It would seem probable, therefore, that a scarcity of twin births
at lambing time is the direct consequence of an abnormally
low number of ripe follicles in the ovary at tupping time (i.e.
during the sexual season). A low percentage of twins is generally
associated with barrenness, a fact which is recognised by flocks
masters, and which is proved very clearly by Heape's statistics.
And since ewes which are constitutionally barren are a rarity,
there can be little doubt that infertility among sheep is due
ordinarily to an absence or great scarcity of follicles available for
ovulation at tupping time.
Scarcity of mature follicles must itself result either from a
retardation in follicular development or from an unusual tendency
towards follicular degeneration whether occurring shortly before
the sexual season or at some previous period in the animal's
lifetime. Atretic or degenerate follicles are by no means un-
common in sheeps' ovaries, the process of atresia appearing to
set in most commonly in follicles which have reached a size
varying from about one-eighth to one-half the dimensions of the
mature follicle. It may set in, however, at practically any stage
of development and probably in the so-called primordial follicle
(see p. 156). There can be little doubt that an excessive follicular
degeneration results usually from an insufficiency of stimulating
power at the disposal of the ewe.
That a relative scarcity of ripe follicles in sheeps' ovaries
at the sexual season is due to retardation of development is a
conclusion which is based on inference rather than observation,
for little is known regarding the actual rate of growth of the
Graafian follicle. Nevertheless, there is every reason for sup-
posing that the processes of growth and maturation can be
very largely influenced both by insufficiency of food supply on
the one hand and by artificial stimulation on the other. This
fact has been recognised for years past by certain individual
flockmasters who have consistently practised the methods of
" flushing " or artificially stimulating their ewes by means of
an extra supply of special food at the approach of the tupping
season, but no precise records of the effects of this process had
been published until lately, when the Highland and Agricultural
Society of Scotland undertook an investigation upon this
subject.
598 THE PHYSIOLOGY OF REPRODUCTION
In the report which has since been issued,1 and which contains
the lambing statistics for various flocks of Scottish sheep for
the years 1905, 1906, and 1907, it is shown that the percentage
of lambs born was, as a general rule, highest among sheep
which had been subjected to a process of artificial stimulation.
The method adopted was to feed the ewes upon turnips, oats,
maize, dried grains, or other additional food at the tupping
time and for about three weeks previously, while maintaining
them upon grass only during the greater part of the year. Some
flocks, however, received a limited supply of extra food
(generally turnips) during gestation, and especially during the
later part of this period. The additional supply of turnips,
which are specially rich in carbohydrate material, was found
to be in no way detrimental to fertility, but rather the reverse,
when accompanied by other food (pasture), and so not taken in
excess. The statistics show that in the flocks treated in the
way described, the percentage of lambs per ewes 2 was almost
invariably in excess of the average percentage for flocks which
received no special treatment, while the percentage of barren
ewes was usually also less in the specially fed flocks. In some
cases the number of lambs per ewes in the flushed flocks was
nearly 200 per cent. Among flocks belonging to the same
breeds (Border Leicester or half-bred Border Leicester) which
received no sort of special treatment, the average proportion
of lambs per ewes was between 150 and 160 per cent., while
flocks which were run upon superior pasture at the approach
of the sexual season, without being otherwise specially fed,
generally produced a slightly larger percentage of lambs. The
twins appear almost invariably to have been born early during
lambing, thus showing that the generative activity of the ewes
tends to be greatest at the commencement of the sexual season.
It has proved more difficult to obtain definite information
concerning the effects of flushing in one year upon the fertility
of the ewes in subsequent seasons. The more usual experience
of flockmasters seems to be that flushing is not in any way
prejudicial to breeding stock unless it is overdone, the object
1 Marshall, "Fertility in Scottish Sheep," Trans. Highland and Agric.
Soc., vol. xx., 1908. See also Proc. Roy. Soc., B., vol. Ixxvii., 1905.
2 That is to say, the number of lambs per 100 ewes.
FERTILITY 599
of the process being to get the animals in an improving condition
without permitting them to put on too much fat. If the
artificial feeding is excessive and the sheep are forced to depend
for the remainder of the year upon a mere sustenance diet, it is
easy to understand that they would tend to deteriorate, antt~
their subsequent fertility become impaired, owing probably to
a higher frequency of follicular degeneration. It is seemingly
for such a reason that some flockmasters regard the practice of
flushing as one altogether to be deprecated. There is some
evidence, however, that if sheep are specially fed in one season,
the process must be repeated in the next, and that if this is
omitted the sheep tend to be less fertile than if they had never
been subjected to flushing.
It has already been mentioned (p. 335) that the practice of
flushing tends to hasten the sexual season, the sheep coming
" on heat " sooner than they would otherwise. The result
must be ascribed to a general increase in the ovarian meta-
bolism consequent upon the stimulating power of the special
food supply. Conversely, it has been shown that in ewes which
are poorly fed the sexual season is often retarded, and the
fertility of the flock reduced. So also the occurrence of a snow-
storm, or other unfavourable climatic condition, occurring during
tupping time will cause a corresponding scarcity of twin births
in the following lambing season. There can be little doubt,
therefore, that the conditions which exist during tupping time
are largely responsible for controlling the fertility of the flock,
and that favourable conditions tend to promote the more rapid
growth and maturation of the follicles in the ovary, and cause a
greater number to discharge their ova during the oestrous periods.
It would appear also that the condition of the ewe is a far
more important factor in determining the number of twin births
than that of the ram ; but it is obvious that the number of ewes
which one ram can serve successfully must depend upon the
degree of vigour possessed by the latter. Sixty ewes to one
ram is about the usual proportion allowed.1
1 It is said that a good stallion should be able to serve eighty mares in
one season, and get on an average forty to fifty foals. See Wallace, loc. cit.
The reproductive capacity of the male animal is almost invariably far
greater than that of the female.
600 THE PHYSIOLOGY OF REPRODUCTION
EFFECT OF PROLONGED LACTATION
It has been recorded that the continuance of lactation
commonly exerts an inhibitory influence on menstruation in
women and on heat in animals, though this is very far from being
invariable (see p. 74). There can be no doubt that in the case
of sows, for example, early weaning is conducive to a more
frequent recurrence of oestrus and an increased number of
litters (see p. 50). In a similar way long-continued lactation
is believed to reduce the fecundity of women, who sometimes
refrain from weaning their babies in the belief that by so doing
they are less liable to become pregnant again. Moreover,
Haddon's observations l upon the Eastern Islanders of the
Torres Straits show that with these people also prolonged nursing
tends to reduce the size of the families, and that a single lactation
may be continued for three years.
EFFECT OF DRUGS
There is little evidence as to the effects of drugs upon egg-
or sperm-production, but innumerable substances have been
recommended as cures for impotence.2 Cantharides and various
other drugs are said to produce sexual excitement, but this result
is probably due simply to the increased flow of blood to the
generative organs which these substances induce.3 Wallace says
that the practice adopted by some grooms of giving cantha rides
to stallions is strongly to be deprecated. Bloch is disposed to
recommend the use of phosphorus and strychnine in the treat-
ment of impotence in men, but the most favourable results have
been obtained by yohimbine, an alkaloid prepared from the bark
of a West African tree. Bloch mentions several cases where, in
his own experience, treatment by yohimbine has been entirely
successful, and there are numerous others on record. Many
1 Haddon, Reports of the Cambridge Anthropological Expedition to Torres
Straits, vol. vi., Cambridge, 1908.
2 For the distinction between sterility and impotence see below (p. 606).
3 Bloch, The Sexual Life of our Time, English Translation, London,
1908.
FERTILITY 601
veterinarians also have testified to the powerful aphrodisiac
action of yohimbine, stating further that it is capable of inducing
a condition of heat in domestic animals and acting as an effective
remedy for certain kinds of sterility.
Daels l found that yohimbine when administered to dogs ~
produced hypersemia of the generative organs, followed by
mucous and sanguineous discharge, but not true heat. Dr.
Cramer and the present writer 2 have made similar observations.
We first administered O005 grams of yohimbine twice daily for
nearly a fortnight to each of two anoestrous bitches, the drug
being swallowed in the form of tablets. Marked congestion of
the generative organs followed. On treating rabbits with yohim-
bine the vulva and the uterine mucosa became excessively
hypersemic, the entire generative tract being affected to some
extent. The ovaries were much overgrown by luteal tissue,
and degenerate follicles which are generally so common in rabbits'
ovaries, were relatively scarce. " It seems extremely probable,
therefore, that yohimbine, by preserving a constant and rich
supply of blood, and consequently of nutriment, to the ovaries,
may arrest the normal process of follicular degeneration, and so
be the means of bringing a larger number of follicles to maturity
than would otherwise be the case, thereby tending to increase
the fertility/' There was some evidence also that yohimbine
may promote mammary development and the secretion of milk.
EFFECTS OF IN-BREEDING AND CROSS-BREEDING
The fact that in-breeding may result in a reduced fertility
has been already discussed in dealing with the significance of
the fertilisation process (pp. 207-214). It was then pointed out
that a tendency towards sterility is often associated with a con-
stitutional loss of vigour. In the same place it was mentioned
further that cross fertilisation between organisms which are
allied but belong to different strains often results in an increased
1 Daels, "On the Relation between the Ovaries and the Uterus," Surgery
Gynaecology and Obstetrics, vol. vi. (Feb.), 1908.
2 Cramer and Marshall, " Preliminary Note on the Action of Yohimbine
on the Generative System," Jour. Econ. Biol., vol. iii., 1908.
602 THE PHYSIOLOGY OF REPRODUCTION
fertility,1 but that cross fertilisation between different species
is frequently difficult to accomplish while there is every gradua-
tion between a mere disinclination towards gametic union and
complete cross sterility.
The differences in fertility between varieties and species
when crossed are discussed at some length by Darwin,2 who
summarises his general conclusions under seven heads. Firstly,
the laws governing hybridisation in plants and animals are
practically identical. Secondly, there are all degrees of cross
infertility. :e Thirdly, the degree of sterility of a first cross
between two species does not always run strictly parallel with
that of their hybrid offspring. Many cases are known of species
which can be crossed with ease, but yield hybrids excessively
sterile ; and conversely some which can be crossed with great
difficulty, but produce fairly fertile hybrids. This is an inex-
plicable fact on the view that species have been specially
endowed with mutual sterility in order to keep them distinct/'
Fourthly, the degree of sterility is often different in the two
sorts of reciprocal crosses between the same species, and hybrids
produced from reciprocal crosses sometimes differ in their degree
of sterility. " Fifthly, the degree of sterility of first crosses
and of hybrids runs, to a certain extent, parallel with the general
or systematic affinity of the forms which are united. For
species belonging to distinct genera can rarely, and those
belonging to distinct families can never, be crossed. The
parallelism is, however, far from complete ; for a multitude
of closely allied species will not unite, or unite with extreme
difficulty, whilst other species, widely different from one another,
can be crossed with perfect facility. Nor does the difficulty
depend on ordinary constitutional differences, for annual and
perennial plants, deciduous and evergreen trees, plants flowering
at different seasons, inhabiting different stations, and naturally
living under the most opposite climates, can often be crossed
with ease. The difficulty or facility depends exclusively on the
1 Frazer has shown that this fact is probably the biological basis for the
practice of exogamic marriages originally adopted by primitive races of
mankind and perpetuated under the influence of natural selection (Totemism
and Exogamy, London, 1910).
2 Darwin, loc. cit, See also Origin of Species, 6th Edition, London,
1872,
FERTILITY 603
sexual constitution of the species which are crossed ; or on
their elective affinity/' Sixthly, cross sterility between species
may depend possibly in certain cases upon distinct causes,
such as deterioration due to unnatural conditions to which the
hybrid embryo may be exposed in the uterus, egg, or seed Trf
the mother. " Seventhly, hybrids and mongrels present, with
the one great exception of fertility, the most striking accordance
in all other respects ; namely, in the laws of their resemblance
to their two parents, in their tendency to reversion, in their
variability, and in being absorbed through repeated crosses by
either parent form/' It is obvious, however, that this last
conclusion requires some modification in the light of recent
Mendelian research.
Darwin maintains further that the cross fertility which
exists between the different varieties of various species of
domesticated animals, in spite of their great divergence in
external appearance, is the direct effect of domestication which
eliminates the tendency towards mutual sterility. In this way
" the domesticated descendants of species, which in their natural
state would have been in some degree sterile when crossed,
become perfectly fertile together/' Both Darwin and Wallace
lay stress upon the apparent existence of a parallelism between
crossing and change of conditions in so far as these affect the
power to reproduce. " Slight changes of conditions and a slight
amount of crossing, are beneficial ; while extreme changes, and
crosses between individuals too far removed in structure or
constitution, are injurious/' * Furthermore, domestic animals
are less susceptible to the influences of changed conditions of
existence than wild animals, a fact which finds a parallel in the
absence of sterility between domesticated varieties of the same
species.
Wallace has cited several cases in which it has been shown
that hybrids between distinct species are fertile inter se. Such
cases are the hybrids between the domestic and Chinese geese,
those between the Indian humped and common cattle, and the
various hybrids between the different species of the genus Cams.
A recently recorded case of a fertile hybrid between a lion
and a jaguar may also be cited. These and other observations
1 Wallace (A. R.), Darwinism, London, 1897.
604 THE PHYSIOLOGY OF REPRODUCTION
show that sterility among hybrids between closely allied species,
although usual, is very far from being universal.1 Similar cases
have been recorded from among plants.
The cause of sterility in hybrid organisms is still to a large
extent an open question. In some cases the generative organs
are atrophied or imperfectly developed, while in most, if not
all sterile hybrids, the gametes are not developed. For example,
IwanofE 2 states that hybrids between the horse and the zebra
do not possess spermatozoa.
It has been suggested that the sterility is due to irregularities
in the mechanics of division in the germ cells. " When we recall
that at one stage in the development of the germ cells there
may be a pairing and subsequent fusion of the maternal and
paternal chromosomes, we can readily imagine that any differ-
ences in their behaviour at this time might lead to disastrous
results." 3
INHERITANCE OF FERTILITY
That fertility is a racial characteristic, and consequently is
capable of hereditary transmission, is a fact that is generally
accepted. Among sheep, for example, some breeds, like the
Dorset Horns, the Hampshire Downs, and the Limestones, are
notoriously prolific, while other varieties, like the Scotch Black-
faced, are relatively infertile.4 Furthermore, there is a con-
siderable amount of evidence that in each breed there are
particular strains of related individuals which have a higher
degree of fertility than the average, and that flockmasters, by
breeding from twin ewes and employing the services of twin rams,
have been able permanently to increase the fertility of their stock.5
1 See Suchetet, " Problemes Hybridologiqges," Jour, de VAnat. etla Phys.,
vol. xxxiii., 1897 ; Dewar and Finn, The Making of Species, London, 1909.
3 Iwanoff, " Untersuchungen iiber die Unfruchtbarkeit von Zebroiden,"
Biol. Cent., vol. xxv., 1905. "De la Fecondation Artificielle chez les Mammi-
feres," Arch, des Sciences Biologiques, vol. xii., 1907.
3 Morgan, Experimental Zoology, New York, 1907.
4 The Leicester breed of sheep is characterised by a relatively low fertility,
and this is said to be due to the preference that was shown to large single
lambs at the time when high prices ruled, and the consequent discarding
of ewes which bore twins. See Wallace (R.), loc. cit.
5 Marshall, " Fertility in Scottish Sheep," Trans. Highland and Agric.
Soc., vol. xx., 1908.
FERTILITY 605
The inheritance of fertility in Man and also in thoroughbred
horses has been investigated statistically by Karl Pearson and
his biometrical collaborators,1 to whose memoir the reader is
referred for a full discussion of the mathematical details and
the conclusions which are arrived at. It is there shown,
among other facts, that the woman inherits fertility equally
through the male and female lines. Among thoroughbred
race-horses the fecundity was first ascertained (i.e. the ratio
of foals surviving to be yearlings to the total number of foals
possible under the given conditions), and the following general
conclusions were afterwards reached : — (1) Fecundity is inherited
between dam and daughter, and (2) Fecundity is also inherited
through the male line, i.e. the sire hands down to his daughter
a portion of the fertility of his dam. Thus fecundity, which is,
of course, a latent character in the male, was measured for a
horse and for his sire, and was found to be strongly inherited.
More recently Rommel and Phillips 2 have shown mathe-
matically that there is an actual correlation between the size of
the litter in two successive generations of Poland China sows,
the productiveness being a character which is transmitted from
mother and daughter.
On the other hand Pearson,3 from studying Weldon's records
of mice-breeding experiments, failed to find a sensible parental
correlation in regard to the size of the litters. Furthermore,
Pearl and Surface,4 as a result of a statistical investigation on
egg-production in Barred Plymouth Rock fowls, carried on over
nine years, found no evidence of the inheritance of fecundity.
For this particular breed at any rate the capacity for egg-pro-
ducing could not be increased by selective breeding, but tended
1 Pearson, Lee, and Bramley-Moore, " Mathematical Contributions to the
Theory of Evolution : VI., Genetic (Reproductive) Selection, Inheritance of
Fertility," &c., Phil. Trans., A., vol. cxcii., 1899.
2 Rommel and Phillips, "Inheritance in the Female Line of Size of
Litter in Poland China Sows," Proc. Amer. Phil. Soc., vol. xlv., 1907.
3 Pearson, " On Heredity in Mice, from the Records of the late W. F. R.
Weldon," Biometrika, vol. v., 1907.
4 Pearl and Surface, " Data on the Inheritance of Fecundity obtained
from the Records of Egg Production," &c., Maine Agric. Exp. Station,
Bulletin No. 166; Maine, 1909. Pearl, "A Biometrical Study of Egg Pro-
duction in the Domestic Fowl," U. S. Dep. of Agric., Bureau of Animal
Industry, Bulletin No. 110; Washington, 1909.
606 THE PHYSIOLOGY OF REPRODUCTION
rather to diminish, though, the last result may have been due to
slight environmental changes. It is possible that fertility, like
other characteristics, cannot be increased indefinitely by selective
breeding, but that when once the limit existing in the strain
has been reached, artificial selection is powerless to effect an
improvement.
CERTAIN CAUSES OF STERILITY
A detailed account of the various pathological conditions
which are capable of inducing sterility is outside the scope of this
work. The medical publications dealing with the subject form
a very considerable literature,1 while the causes of sterility in
animals are discussed, though somewhat unsatisfactorily, in
many of the veterinary text-books. It may not be out of
place, however, to refer briefly to certain of the conditions
which are known to induce sterility in Man and also in
animals.
In the case of the male an incapacity to procreate is due
either to impotence (i.e. inability to perform the sexual act),
or to sterility (using the term in the more restricted sense,
implying an absence of spermatozoa). Impotence may result
from (1) absence of sexual desire, (2) absence of the power of
erection and consequent intromission, (3) absence of the power
of ejaculating the seminal fluid into the vagina, and (4) absence
of the ability to experience pleasure during the act of coition,
and at the time of the emission of the semen.2 Or, according
to another classification, the causation of impotence may be
either anatomical, physiological, pathological, or psychological.
Among the anatomical causes may be mentioned defects and
deformities in the penis. The physiological and pathological
causes include incomplete erections, premature ejaculations,
diseases of the brain and spinal cord (and more particularly of
the centres for the performance of the sexual act), besides such
diseases as albuminuria or prolonged diabetes. The psycho-
logical causes include fear, repugnance, want of confidence, &c.3
1 Miiller (P.), Die UnfruchtbarJceit der Ehe, Stuttgart, 1885. This work
contains a bibliography.
2 Hammond, Sexual Impotence in the Male, New York, 1883.
3 Corner, Diseases of the Male Generative Organs, London, 1907.
FERTILITY 607
Complete sterility, i.e. inability to procreate owing to the
absence of fertile semen, is due to various causes, and may be
either congenital or acquired. Congenital sterility occurs when
the testicles are never developed, or are so imperfectly de-
veloped that they fail to produce ripe spermatozoa. In cases of
incomplete descent of the testicles fertility is rare, but it may
exist for a short time as in young men from twenty to twenty-
three years of age. Acquired sterility results from the various
diseases to which the generative organs are subject, such as
tubercle, syphilis, attacks of inflammation, urethral stricture,
epididymitis, prostatic enlargement or diminution, &C.1
A more special cause of sterility in men is one which operates
in the case of workers with radium or the Rontgen rays. Several
years ago Albers-Schonberg 2 noticed that the X-rays induced
sterility in guinea-pigs and rabbits, but without interfering with
the sexual potency. These observations have been confirmed
by other investigators,3 who have shown, further, that the
azoospermia is due to the degeneration of the cells lining the
seminal canals. In men it has been proved that mere presence
in an X-ray atmosphere incidental to radiography sooner or
later causes a condition of complete sterility, but without any
apparent diminution of sexual potency.4 As Gordon observes,
for those working in an X-ray atmosphere adequate protection
for all parts of the body not directly exposed for examination
or treatment is indispensable, but, on the other hand, the X-rays
afford a convenient, painless, and harmless method of inducing
sterility, in cases in which it is desirable to effect this result.5
1 Corner, loc. cit.
2 Albers-Schonberg, " Ueber eine bisher unbekannte Wirkung der Rontgen-
strahlen auf den Organismus der Tiere," Munchener med. Wochenschr., No.
43, 1903.
3 See Gordon, "Diseases caused by Physical Agents," Osier's System
of Medicine, vol. i., London, 1907. See also Regaud and Dubreuil, "Action
des Rayons de Rontgen sur la Testicule de la Lapin," C. R. de la Soc. de
BioL, vol. Ixiii., 1907.
4 Brown and Osgood, " X-Rays and Sterility," Amer. Jour, of Surgery,
vol. xviii. (April), 1905.
5 Gordon, loc. cit. It has been shown also that the Rontgen rays may
induce degeneration of the follicles, corpora lutea, and interstitial cells in
the ovaries and cause sterility in the female. See Bourn, Ancel, and Villemin
(C. R. de la Soc. de BioL, vol. Ixi., 1906), Bergomie and Trabondeau (C. R. de la
Soc. de Biol., vol. hdi., 1907), and Specht (Arch. f. Gyndk., vol. Ixxviii. 1907).
608 THE PHYSIOLOGY OF REPRODUCTION
The various causes of sterility in women are discussed at
considerable length by Kelly,1 as well as by other writers 2 on
gynaecology. Kelly mentions the following conditions as likely
to be found associated with sterility : Gonorrhceal infection of
Skene's or Bartholin's gland, stricture of the vagina or cervix,
the presence of a uterine polyp, a uterine fibroid tumour, a
parovarian cyst, or a nodular salpingitis (from gonorrhoea or
tuberculosis), atresia of the uterine tube (from inflammation),
and the existence of ovarian adhesions. These, and other
causes of sterility, and the methods of treatment to be
adopted, are fully dealt with by Kelly.
Sterility in animals, as in Man, is brought about by a variety
of causes,3 some of which are incurable, but others, such as
constriction of the os uteri, are capable of treatment. In the
case of cattle great difficulty is often experienced in getting the
cows to breed after attacks of contagious abortion, and this is
said to be due to an acid condition of the vaginal mucous
membrane. In order to remedy this, injections of dilute solu-
tions of bicarbonate of soda are employed and are found to
be effective. Others recommend that the uterus should be
injected with solutions of perchloride of mercury.4
Sterility in mares and cows and other animals is often due to
structural or functional defects in the vagina, os uteri, or cervix.
These may sometimes be overcome by resorting to artificial
insemination, the methods of which are described below.5
Furthermore, sterility among cows may be contagious owing
to the disease known as infectious granular vaginitis, which is
primarily an acute inflammation of the vulva and vagina. It is
1 Kelly, Medical Oynecology, London, 1908.
2 See especially Duncan, Sterility in Women, London, 1884, and
Miiller, loc. cit. Duncan states his opinion that probably ten per cent,
of the marriages in Great Britain are sterile.
3 Fleming, Text-book of Veterinary Obstetrics, London, 1878.
4 Wallace (R.), loc. cit. According to Knowles ("Sterility of Mares and
Cows," Amer. Veterinary Review), " sub-acute and chronic cervical hyperasmia
are probably the most frequent and fruitful causes of temporary sterility,
due in an astonishingly large number of instances to continually recurring
abortions."
5 Constriction of the os uteri in cows may often be remedied by the
employment of a large probe followed by the finger, or better still by a
specially devised instrument known as a dilator. See Wallace (R.), loc. cit.
FERTILITY 609
commonly communicated by a contaminated bull in which the
penis and sheath are affected. Similarly a bull may become
diseased by serving an infected cow, and in this way vaginitis
may spread through an entire herd. During recent years con-
tagious sterility has been very common in Switzerland ancT
Germany, and there is evidence of its existence in England.
Antiseptic disinfection is useful, but experience has shown that
even when treated infectious vagin'tis often runs a prolonged
course. Nevertheless, a complete cure usually takes place after
some months, this recovery being indicated by the cessation of
the muco-p:rulent discharge and the recurrence at normal
intervals of the cestrous periods.1
Deficient, excessive, or unfavourable nutrition, change of
environment, in-breeding, &c., as sources of infertility, have
been already discussed.
ARTIFICIAL INSEMINATION AS A MEANS OF OVER-
COMING STERILITY
Artificial insemination as a means of overcoming certain
forms of sterility has been employed by various medical men
from Hunter's time downwards. In the case treated by
Hunter himself,2 the husband of the woman experimented upon
was affected with hypospadias. The semen was injected into
the vagina, conception followed, and a child was afterwards
born. Sims 3 recorded a case of a woman who suffered from
dysmenorrhoea and a deformed uterus, and who had been
married for nine years without having children. Artificial in-
semination was resorted to, pregnancy ensued, and a child was
born in due time. Numerous other cases are cited by Heape 4
and Iwanoff,5 to whose papers the reader is referred for biblio-
graphies of the subject.
1 McFadyean, "Sterility in Cows," Jour. Royal Agric. Soc., vol. Ixx.,
1909.
2 This case is described by Home, Phil. Trans., 1799. (See p. 189,
Chapter V.)
3 Sims, Notes Cliniques sur la Chirurgie Uterine, Paris, 1866.
4 Heape, "The Artificial Insemination of Mammals," &c., Proc. Roy. Soc.,
vol. Ixi., 1897.
5 Iwanoff, "De la Fecondation artificielle chez les Mammiferes," Arch,
des Sciences Biologiques, vol. xii., 1907.
2Q
610 THE PHYSIOLOGY OF REPRODUCTION
The method adopted by gynaecologists who have practised
artificial insemination is to inject seminal fluid into the uterus
by means of a syringe, the fluid in most cases being obtained
from the vagina of the same individual shortly after coitus.
In this way it has been found possible to overcome such
structural defects as constriction or undue rigidity of the cervix
or hypertrophy of the lips of the external os uteri. By modify-
ing the method by which the semen is obtained, it has proved
possible to induce pregnancy in cases of abnormal vaginal
secretion where the spermatozoa are ordinarily killed before they
can effect an entrance into the uterus, and in other cases where
there is an inability on the part of the vagina to retain the
semen after coitus.
Artificial insemination has frequently been practised on
mares with a view to overcoming certain forms of sterility, and
considerable success has been attained. " Such defects as
flexion or constriction of the canal of the cervix ; rigidity of
the cervix ; hypertrophy of the lips of the external os, and the
formation of false membranes which may effectually close the
orifice ; inability to retain spermatozoa in the vagina, owing to
abnormal shortness of the organ or to violent muscular con-
traction after coitus ; a want of sufficient muscular power ;
abnormal structure or size of the cervix or os uteri, which pre-
vent the free action of the functions of the cervix ; occlusion of
the os owing to spasmodic contraction of the muscles of the
cervix during coitus ; abnormal or excessive vaginal secretions,
which may kill or deleteriously affect the spermatozoa, &c.,
may be overcome by artificial insemination/' l Heape, and
more recently Iwanoff,2 have cited numerous cases in which
mares have been got in foal successfully by artificial
insemination.
The actual methods employed are described by these writers.3
The most usual plan is to allow the stallion to serve the mare in
the ordinary way, and then, immediately afterwards, to insert
1 Heape, "The Artificial Insemination of Mares," Veterinarian, 1898.
2 Iwanoff, loc. cit. This important memoir, besides containing descrip-
tions of the author's own experiments, gives a very full account of the
literature of artificial insemination.
**' See also a booklet edited and published by Huish, The Cause and
Remedy for Sterility in Mare, Cows, and Bitches, London.
FERTILITY 61 1
a syringe into the vagina, and draw up into it some of the
seminal fluid which is caused to collect in a depression or pocket
made in the vaginal floor by the pressure of the finger tips.
The same mare can then be inseminated by injecting the fluid
so obtained into the uterine cavity, or the semen can be utilised
for impregnating other mares. Another method is to collect
the semen in gelatine capsules which are placed in the vagina
before coitus, and then, when they have been filled, to close
their lids and insert them in the interior of the uterus, where
the heat of the body gradually melts the gelatine and sets free
the spermatozoa. By such means as this several mares may
be impregnated as a result of one service by a stallion. In some
cases pieces of sponge have been employed instead of gelatine
capsules. In transferring semen from one animal to another
it is of considerable importance to preserve a moderate degree
of warmth ; otherwise the spermatozoa are liable to die as a
result of exposure before injection has been effected.
Artificial insemination has been of considerable use also in
remedying sterility in cows as well as in dogs.1
Several investigators by employing artificial insemination
have been successful in getting crosses between animals be-
longing to varieties in which the disparity in size is so great
that coitus between them is difficult or impossible. Thus,
Plonnis 2 in 1876 successfully inseminated a lap-dog with the
semen of a setter, and obtained a pup which in most of its points
resembled its father. Allbrecht 3 performed a similar experi-
ment and obtained a similar result. More recently Heape 4
has described some experiments carried out by Millais, in which
bloodhounds were inseminated with spermatozoa obtained
from Basset hounds (a much smaller breed), litters of cross-bred
pups being produced.
Iwanoff 5 has recorded an experiment in which he successfully
inseminated a white mouse with the spermatozoa of a white rat.
1 See Huish, loc. cit.
2 Plonnis, " Kiinstliche Befruchtung einer Hunden," &c., Inaug. -Dissert.,
Eostock, 1876.
3 Allbrecht, "Kiinstliche Befruchtung," Wochenschr. f. Thierheilkunde
und Viehzucht, Jahrg. xxxix. -s
4 Heape, "The Artificial Insemination of Mammals," Proc. Roy. Soc.,
vol. Ixi., 1897. 5 Iwanoff, loc. cit.
612 THE PHYSIOLOGY OF REPRODUCTION
Two hybrid young ones were produced after a pregnancy lasting
twenty-seven days. They were intermediate in size between
rats and mice. This is the first record of a cross being obtained
between two species so different in size as the rat and the mouse,
coitus between them being practically impossible. Furthermore,
Iwanoff has successfully employed artificial insemination to
obtain hybrids between horses and zebras (a cross which is often
difficult to get by the normal method owing to the liability of
the animals to refuse service).
ABORTION
Abortion is often an important factor in determining a low
fertility, but its frequency of occurrence shows a considerable
range of variation.
With women the frequency of abortion to birth at full term
is said to be from one in five to one in ten.1 According to the
records of Franz 2 for the maternity hospital at Halle, the per-
centage of cases in which abortion occurred was 15*4. Williams 3
expresses the opinion that in ordinary private practice every
fifth or sixth pregnancy usually ends in abortion, and that the
percentage would be considerably increased if one reckoned
the early cases in which there is a profuse loss of blood following
a retardation of the menstrual period, the actual fact of abortion
being often obscured.
Excepting in the case of sheep, there are no satisfactory
data on which to estimate the frequency of abortion among the
different kinds of domestic animals, but there can be no doubt
that it is of common occurrence, and that it occasions much
loss to breeders. For various varieties of English sheep Heape 4
found that the percentage of abortion experienced by 300 flock-
masters varied from nothing to 23*75, while the percentage for
85,878 ewes was 2 '39. The statistics showed that Dorset Horn
and Lincoln breeds suffered most from abortion, the losses from
1 Kelly, loc. cit.'
2 Franz, " Zur Lehre des Aborts," Hegar's Beitrdge, vol. i., 1898.
3 Williams, loc. cit.
4 Heape, "Abortion, Barrenness, and Fertility in Sheep," Jour. Royal
Agric. Soc., vol. x., 1899.
FERTILITY 613
this cause being respectively 4'11 per cent, and 4 per cent. The
Southdown breed were found to occupy an intermediate position
(the percentage of abortion being 2 '86 per cent.), while the other
breeds investigated showed a smaller percentage of abortion.
Among Scottish breeds the percentage of aborting ewes does :
not generally exceed 2 per cent., as far as could be ascertained ;
but with Blackfaced ewes it may be as much as five, or even
a considerably higher number, as a consequence of any special
adverse circumstance.1 It is possible, however, that the per-
centages of abortion are actually somewhat higher than they
appear, since its occurrence during the early stages of pregnancy
is not readily detected, and consequently some of the ewes
which were entered in the statistical returns as barren may
in reality have aborted.
Among cattle in Great Britain the frequency of abortion,
according to Heape,2 is not less than ten per cent, of the total
number of animals selected for breeding, and there can be
no doubt that in certain districts it is often very much higher,
especially where contagious or epidemic abortion occurs. Heape
states further that from ten to twelve per cent, of abortion is
not unusual in herds in which no contagious abortion is proved
to exist.
There are no data available on which to compute the fre-
quency of occurrence of abortion among horses, but the ex-
perience of breeders shows that the losses arising from this
cause are very considerable, and that they are greatest amongst
the better-bred animals. One of the earlier reports of the
Royal Commission on Horse-Breeding stated that in this country
in any given year no less than forty per cent, of the mares
chosen for breeding fail to produce foals, but to what extent
this result is due to sterility or how far it may be ascribed to
abortion does not appear to have been ascertained.
The causes of abortion are diverse, and may be mechanical,
psychological, physiological, or pathological. Deliberate abor-
tion among civilised European nations is a criminal offence
punishable by law, but nevertheless is not infrequently carried
1 Marshall, "Fertility in Scottish Sheep," Trans. Highland and Agric.
Soc., vol. xx., 1908.
2 Heape, The Breeding Industry, Cambridge, 1906.
614 THE PHYSIOLOGY OF REPRODUCTION
out. In Oriental countries and among savages abortion is
practised more openly. The more usual means are drugs (ergot,
ethereal oil of juniper, yew, turpentine, camph r, cantharides,
aloes, &c.),' but none of these are infallible, and owing to their
toxic properties their use is often accompanied by danger.
Haddon '- says that among the Eastern I landers of the Torres
Straits abortion is procured by the leaves of the shore convol-
vulus and certain other plants. Also the old women give the
younger women young leaves of the argerarger (Callicarpa sp.),
a large tree with inedible fruit, and bok, a large shrub. When
a woman's body is saturated with the j ice from the leaves,
she is believed to be proof against fecundity, and can indulge in
sexual intercourse without fear of becoming pregnant. Pro-
bably the toxic substances introduced cause abortion at very
early stages of pregnancy, or even inhibit pregnancy at the ^ ery
outset. Abortion is sometimes procured by purely mechanical
means — e.g. blows, massage, hot injections,3 carrying heavy
loads,4 &c. But although mechanical and psychological influ-
ences, both voluntary and involuntary, play a part in bringing
about abortion, they are probably less frequently concerned
in the process than pathological conditions existing either
in the embryo or in the maternal organism.
Among the causes of abortion in women Kelly 5 mentions
haemorrhage of the chorion, imperfect vascularisation of the
amnion, hydatiform degeneration of the chorion, circulatory
disturbances caused by heart lesions in the mother, various
infections of the mother (notably syphilis), psychic disturbances,
and excessive cohabitation, acute poisoning (by alcohol, phos-
phorus, lead, &c.), and various diseases of the generative organs,
such as endometritis, decidual inflammation, polypoid thicken-
ing, &c. It is stated that the excitability of the nerve centres
which control the movements of the uterus and the tendency
to uterine congestion are greatest at the epochs which would
have been menstrual periods if pregnancy had not occurred,
and consequently that abortion is especially common at these
i Bloch, loc cit. 2 Haddon, loc. cit.
3 Bloch, loc. cit. 4 Haddon, loc. cit.
5 Kelly, loc. cit. See also Oliver, " The Determinants of Abortion," Brit.
Med. Jour., November 30, 1907.
FERTILITY 615
dates.1 The membranes are usually cast off with the foetus,
but the decidua is said in some cases to remain, and to regenerate
a normal uterine mucosa. The expulsion of the foetus and
membranes is accompanied by " pains " comparable to those
occurring in normal parturition, the two processes having a
general similarity, which is closer if abortion takes place in the
later part of pregnancy. There is generally also a considerable
loss of blood. After the expulsion the haemorrhage and pains
cease, and a process of puerperal involution sets in.
In horses abortion is probably most frequent during the
period from the sixth to the ninth week of pregnancy. This is
explained by Ewart 2 as being due to the fact that about this
time the embryo loses its primitive attachment to the uterus
before acquiring its more permanent connection by means of
the allantoic villi, which are only beginning to be numerous.
The yolk sac, which in the marsupial is the organ of foetal
nourishment throughout the whole of pregnancy, in the case of
the horse ceases to provide a sufficient supply at about the end
of the seventh week ; but the horse embryo, instead of being
born at this period, like the marsupial, acquires new and more
efficient structures in the allantoic villi. " At the end of the
third week of gestation, when the reproductive system passes
through one of its periods of general excitement, about one-
fourth of the embryonic sac probably adheres to the uterus ;
but at the end of the sixth week, when another wave of dis-
turbance arrives, all the grappling structures are at one pole.
Hence there is probably more chance of the embryo ' slipping '
at the end of the sixth than at the end of the third week. About
the end of the seventh week the supply of nourishment by means
of the yolk sac is coming to an end, and there is perhaps still
about this time an hereditary tendency for the embryo to escape.
Unless the new and more permanent nutritive apparatus is
provided, unless a countless number of villi rapidly sprout out
from the allantois, the embryo will die from starvation during
the eighth week, and in a few days be discharged. It may
therefore be taken for granted that there is a certain amount
1 Galabin, Manual of Midwifery, 6th Edition, London, 1904.
2 Ewart, A Critical Period in the Development of the Horse, London,
1897.
616 THE PHYSIOLOGY OF REPRODUCTION
of danger at the end of the third and sixth weeks, but that the
most critical period is about the end of the seventh or beginning
of the eighth week ; for unless the villi appear in time, and
succeed in coming into sufficiently intimate relation with the
uterine vessels, the developmental process is of necessity for
ever arrested." 1
Ewart discusses briefly the external conditions and circum-
stances which are likely to lead to abortion, and provides some
useful practical hints as to the best way to treat mares in order
to prevent them from " slipping foal." He remarks that the
horse is a peculiarly high-strung^ nervous animal, and is easily
affected by sudden changes in its surroundings, especially during
the breeding season. Such changes are, no doubt, often re-
sponsible for setting up disturbances in the nervous system,
and so inducing abortion, more particularly at that period of
development at which the fixation of the embryo to the uterine
wall is relatively insecure.
Abortion in cows is said to be commonest during the first
month of pregnancy. According to Wallace 2 the usual causes
are the following : (1) Eating ergotised grass ; (2) injury due
to horning by other cattle, hunting by dogs, or shaking and
bruising in travelling, &c. ; (3) physical strain, resulting from
walking over too soft land, &e. ; (4) very cold or foul water,
or frozen turnips, &c. ; (5) superpurgation, whether occurring
naturally or as a consequence of dosing by physic ; (6) contagion
from other cows affected by epidemic abortion. This is said to
be the commonest and at the same time the most dangerous
cause of abortion.
Bang 3 has shown that contagious, epidemic, or epizootic
abortion in cattle is due to a specific bacillus which he has been
able to isolate and cultivate in oxygenated glycerine-bouillon
or serum-gelatine agar. The germ causes the formation of a
brownish-yellow exudate between the chorion and the mucous
1 Ewart, loc. cit.
2 Wallace (K.), loc. cit. Wallace states that after abortion in cattle the
placenta adheres to the cotyledons, and should be removed artificially ;
otherwise it is liable to undergo a process of rotting, sometimes resulting
in septicaemia and death.
3 Bang (B.), " Infectious Abortion in Cattle," Nat. Vet. Soc., Liverpool,
July 25, 1906.
FERTILITY 617
membrane of the uterus, and more particularly around the
cotyledons, but the affected area may be considerably greater.1
The chief mode of entrance is the vagina (especially during
copulation when the contagion is introduced by the bull's penigr),
but Bang has shown experimentally that the germs may be
carried to the seat of the disease by the blood after intra vascular
injection, and furthermore, that they can be absorbed through
the alimentary canal. Thus, after administering some bouillon
culture to a cow, the placenta was found covered with typical
exudate rich in bacilli. There is some experimental evidence
that cows may acquire immunity to the disease, at least tempo-
rarily. Investigations show also that mares, sheep, goats, dogs,
and guinea-pigs may be infected with the bacillus experimentally,
but in all probability the disease is ordinarily confined to cattle.
The abortion microbe is stated to be oval or rod-shaped, between
one and two microns in length, and non-motile. It sometimes
occurs singly, but in many places the bacilli are collected in dense
groups or colonies. The microbe associated with abortion out-
breaks in sheep is said to be a vibrio and therefore totally different.
It has been isolated and used experimentally to infect pregnant
ewes. Pregnant cows, however, cannot be infected by it.
The external use of antiseptics is said to prevent the
spread of contagious abortion by means of disinfection, and
this is the treatment prescribed by the Board of Agriculture.3
The causes of abortion in sheep are dealt with at some length
by Heape in the paper already referred to.4 Statistical evidence
shows that an excessive proportion of shearling ewes in a flock
is associated with a relatively high percentage of abortion, and
that ewes of particular breeds in certain districts, or run on
certain subsoils, are more liable to abortion than the average
for the breed in question. Thus Lincoln sheep run on the Wolds
suffer much more from abortion than sheep of the same breed
in other districts. The Southdown and Hampshire Down
1 Report of the Departmental Committee appointed by the Board of
Agriculture and Fisheries to inquire into Epizootic Abortion, London, 1909.
2 According to the Keport referred to above, nothing more than a quite
subsidiary r6le in the spread of the disease can now be referred to the bull.
3 Board of Agriculture Leaflet, No. 108, 1904.
4 Heape, "Abortion, Barrenness, and Fertility in Sheep," Jour. Royal
Agric. Soc., vol. x., 1899.
618 THE PHYSIOLOGY OF REPRODUCTION
statistics show that a heavy rainfall during gestation is associated
with a high degree of abortion. Over-exertion (as from jumping
ditches), fright (from strange dogs or shooting), are usually
credited with producing abortion in sheep, but Heape remarks
that such causes are not truly responsible unless the ewes are in
a susceptible condition. The main conclusion reached is that
the food and the resulting condition of the ewes are the principal
factors which influence the percentage of abortion. Unsuitable
food, causing indigestion or other ailments, and poor food, re-
sulting in bad nutrition, are held to be mainly responsible.
Heape states, however, that it is not the kind of food so much as
the condition of the food which is most liable to be at fault,
while the schedules show clearly that a poor condition of ewes
during gestation is associated with a relatively high percentage
of abortion. " Sheep-stained " pasture (i.e. pasture grown
with the aid of sheep manure or on which sheep have been run
for a considerable time previously) is credited with causing
abortion, and there is strong evidence in support of this view
in cases where rank or over-stimulated growth results.1
As already noted, the Dorset Horn and Lincoln breeds of
sheep suffer most from abortion.2 In the case of the former
this may result partly from inbreeding, since Dorset Horn ewes
served by Hampshire Down rams are less liable to " slip lamb "
than those served by rams of their own breed. It is possible,
therefore, that the abortion may be due to a want of vitality
on the part of the developing embryo, the cross-bred young
possessing a superior vigour. Abortion among Lincoln sheep
has been known to reach thirty, forty, or even fifty per cent.,
and so to assume an epidemic form. Wortley Axe,3 who reported
on an outbreak of abortion among the Lincolnshire flocks in the
season of 1882-83, was disposed to attribute it to debility,
arising largely from foot-rot and exposure to cold winds and
1 Abortion in sheep may result from more exceptional causes. Thus
it is recorded that a large proportion of a certain flock of Cheviot ewes
slipped lamb after a gale which blew down a number of Scotch fir-trees,
the abortion resulting, in the owner's opinion, from the animals eating the
branches and bark. See Marshall, loc. cit. 2 Heape, loc. cit.
3 Wortley Axe, " Outbreak of Abortion and Premature Birth in the Ewe
Flocks of Lincolnshire during the Winter and Spring of 1882-83," Jour.
Royal Agric. Soc.t vol. xxi., 1885.
FERTILITY 619
heavy continuous rains, as well as to the feeding of the ewes
on unripe watery roots and unwholesome, filth-laden shells.
Heape has suggested that abortion on the Wolds arises partly
from the practice of unduly crowding the ewes on turnip fields.
As already mentioned; a bacillus has been isolated from outbreaks
of abortion in ewes, and has been used to infect other ewes for
experimental purposes in the laboratory.
THE INCREASE OF FERTILITY, A PROBLEM OP PRACTICAL
BREEDING
Heape l has shown from statistical evidence that the amount
of money invested in live stock in this country cannot be com-
puted at very much less than £450,000,000, and this sum does
not include the enormous capital spent on buildings, land,
vehicles, and various accessories. The annual export of live
stock from Great Britain in recent years has been tending
steadily to increase, until it has reached a total value of £1,750,000.
It is clear, therefore, that in this country the breeding industry
occupies a position of no inconsiderable importance, and that the
scientific study of the problems of breeding possesses a great
national interest. Foremost among these problems is that
which concerns itself with the factors that control fertility.
Despite its comparative prosperity, it is evident that the
breeding industry suffers annually from no inappreciable loss.
Allusion has been made to the losses sustained by breeders
owing to the occurrence of abortion in domestic animals.
Sterility, whether persistent or temporary, is responsible for a
greater reduction of profit. The prevalent barrenness among
the better class of Shire mares has been already referred to,
while incapacity to breed is perhaps still commoner among
thoroughbreds. As already mentioned, the Royal Commission on
Horse-Breeding found that no less than forty per cent, of the
mares chosen for breeding in any given year failed to produce
offspring.2 Moreover, there is evidence that in certain districts
1 Heape, The Breeding Industry, Cambridge, 1906.
2 Owing probably to a combination of circumstances, the number of foals
dropped in this country in recent years has shown a tendency to decrease.
This fact has called forth serious comment in many quarters, and attention
620 THE PHYSIOLOGY OF REPRODUCTION
of India this percentage is still higher.1 Among cattle the
average loss from sterility and abortion (together with mortality
of calves) is estimated by Heape 2 to be at least fifteen per cent.,
while it is shown in the report (already referred to) issued by
the Royal Agricultural Society on fertility in English sheep for
the year 1899, that the proportion of sterile ewes was 4'71per cent,
out of a total number of 96,520, and this percentage does not
include the ewes which aborted (see p. 612). In view of these
facts, it is obvious, as Heape has pointed out, that any means by
which sterility in domestic animals can be checked and their
capacity to bear young increased, must be possessed of great
commercial value.
THE BIRTH-RATE IN MAN ;
It is now more than a century ago since Malthus 3 advanced
his famous proposition that whereas population tends to in-
crease in geometrical ratio, the means of subsistence increase
only in arithmetical proportion. As a consequence of the
acceptance of that doctrine, the political economists of the
early Victorian period tended to see in over-population the
most fruitful source of pauperism, disease, and crime, and the
cause of increasing congestion in the future. That Malthus*
predictions have not been verified is a matter of common
knowledge, and the problem before the modern economist is not
how to place a check on population generally, but rather how
to secure that future generations shall be sufficiently recruited
from that section of the population which is industrially capable.
There is abundant evidence that in most civilised countries
at the present time the birth-rate (that is, the proportion of
the children born to the population) is tending to decrease,
while in some countries the actual population is diminishing.
This decline in the birth-rate has been made the subject of
has been drawn to the urgent need for practical proposals on the subject with
a view to maintaining the horse supply of the country and arresting a state
of things which, if it continues, must be a source of danger.
1 Ewart, loc. cit. 2 Heape, loc. cit.
3 Malthus, An Essay on the Principles of Population, 7th edition,
London, 1872.
FERTILITY 621
statistical inquiries by Newsholme and Stevenson,1 and Udny
Yule.2 These writers have shown that the observed fall is not
simply a consequence of changes in the ages of the people, or in
the proportion of married to single women, for allowing for such
alterations as have occurred, the number of births per 100,000
of the population in England and Wales, for example, has dropped
from 3236 in 1861 to 2729 in 1901.
The decline in the birth-rate (so far as England and Wales are
concerned) is not appreciably greater in the towns than in the
rural districts. It is, however, especially marked in places
inhabited by the servant-keeping class.3 It appears to be
greatest in those sections of the population which give evidence
of the exercise of thrift and foresight, for Heron 4 has shown
that the more cultured, prosperous, and healthy classes are
producing fewer children than those belonging to a lower social
status.
There is no evidence that this decline in the birth-rate is
due to an increase of sterility, for congenital unavoidable sterility
in either sex is rare.5 .The inference is, therefore, that the
decline is principally, if not entirely, the result of deliberate
volition in the regulation of the married state. Direct evidence
that this inference is correct is provided by the Fabian Society,
whose report 6 indicates that the practice of limitation prevails
with at least one-half, if not three-fourths, of all the married
people of Great Britain. The statistics collected from other
countries point in a similar direction.7 This is noticeably the
case for New South Wales, Victoria, and New Zealand among
the British Colonies, and for France among Continental nations.
Indications pointing unmistakably in the same direction are
to be observed in the United States, Germany (especially Saxony,
and certain of the big cities) as well as in Belgium and Italy.
1 Newsholme and Stevenson, " The Decline of Human Fertility in the
United Kingdom," &c., Jour. Royal Statis. Soc., 1906.
2 Yule, " On the Changes in the Marriage and Birth-Kates," &c., Jour.
Roy. Statis. Soc., 1906.
3 Sidney Webb, "The Decline in the Birth-Kate," Fabian Society Tract,
London, 1907.
4 Heron, "On the Relation of Fertility in Man to Social Status," &c.,
Drapers' Company Memoir, London, 1906.
5 Kelly, loc. cit. 6 Sidney Webb, loc. cit.
7 Newsholme and Stevenson, loc. cit.
622 THE PHYSIOLOGY OF REPRODUCTION
The German rural population are apparently still unaffected,
while the British and Irish Catholics are almost so, since any
regulation of the married state is forbidden by their religion,
but in other Catholic countries this prohibition does not appear
to be so strongly insisted on, and is often altogether ignored.
To the political economist of sixty years ago this decline in
the production of children would have been regarded as the
fulfilment of an aspiration, but the modern economist takes a
different view. He believes that a mere limitation of numbers
cannot be a factor in the improvement of social conditions, and
the student of Eugenics never tires of urging that the real
danger before society is not over-multiplication, but multiplica-
tion of the unfit. As Sidney Webb has said : " Modern civilisa-
tion is faced by two awkward facts ; the production of children
is rapidly declining, and this decline is not uniform, but char-
acteristic of the more prudent, foreseeing, and restrained members
of the community. . . . The question is whether we shall be
able to turn round with sufficient sharpness and in time. For
we have unconsciously based so much of our social policy — so
many of our habits, traditions, prejudices, and beliefs — on the
assumption that the growth of population is always to be
reckoned with, and even feared, that a genuine realisation of
the contrary position will involve great changes. There are
thousands of men thinking themselves educated citizens to-day
to whose whole system of social and economic beliefs the dis-
covery will be as subversive as was that announced by
Copernicus. We may at last understand what the modern
economist means when he tells us that the most valuable of the
year's crops, as it is the most costly, is not the wheat harvest
or the lambing, but the year's quota of adolescent young men
and women enlisted in the productive service of the community ;
and that the due proportion and best possible care of this
particular product is of far greater consequence to the nation,
than any other of its occupations." l
1 Sidney Webb, loc. cit. Cf. also Whetham, The Family and the
Nation, London, 1909.
CHAPTER XV
THE FACTORS WHICH DETERMINE SEX
" What was a question once is a question still." — BACON.
A WOKK upon the Physiology of Keproduction would be incom-
plete without some reference to the problem of sex-determina-
tion, and some account of the more recent attempts which
have been made towards its solution. A resume of some of the
more important papers and memoirs is given by Morgan in his
work on Experimental Zoology? and the reader is referred
to this volume for further references and fuller information in
regard to certain of the points discussed. It is hoped, however,
that the present summary may prove useful if only as a supple-
ment to Morgan's discussion, since certain important papers
dealing with sex-determination and containing an account of
experimental investigations have been published since the
appearance of Morgan's volume, and these papers I have en-
deavoured to summarise here. Moreover, some of the more
recent observations, and more particularly those relating to
" parasitic castration/' have necessitated a further revision
of the conclusions previously arrived at.
Reproduction in organisms may occur by simple fission or
budding, in which case it is said to be asexual, or it may involve
the union of two conjugating cells, which in Metazoa and Meta-
phyta are specially differentiated for the purpose, and are known
as ova and spermatozoa. In some animals these two types of
cell are produced by the same individual, which is then said to
be hermaphrodite or monoecious, but such a condition is rare
or absent altogether among the highest forms of life. In the
vast majority of animals there are two sexes — that is to say,
two kinds of sexual individuals, the male and the female, whose
1 Morgan, Experimental Zoology, New York, 1907. See also Geddes
and Thomson, The Evolution of Sex, Kevised Edition, Londoi , 1904,
and Thomson, Heredity, London, 1908.
624 THE PHYSIOLOGY OF REPRODUCTION
respective functions are to produce spermatozoa and ova. This
condition is described as dioecious. Again, in a relatively small
number of animals, of which the bee is a familiar example, there
are three kinds of individuals, perfect females, imperfect females,
and males. In a few insects there are even more than three
kinds. Lastly, in certain of the lower animals the females can
reproduce ova which are capable of developing into adult in-
dividuals without conjugating with spermatozoa. This method
of reproduction is described as parthenogenetic (see p. 216).
Among dioecious animals the two sexual individuals are
generally produced in approximately equal numbers. Thus, in
Man the number of male births is only slightly in excess of the
number of female births, the proportion varying very slightly
in different countries,1 while in those races in which the numerical
proportion of the two sexes among the adult population is very
unequal, inequality is due to a higher death-rate of children
belonging to one sex. Thus among the Todas the pronounced
preponderance of males over females results from the practice
of female infanticide.2
Theories of sex determination may be conveniently arranged
under three headings : — (1) Those in which it is assumed that the
sexual condition of the individual is determined subsequently
to fertilisation and during embryonic or larval life ; (2) those
which assume that sex is established either at the moment of
fertilisation or prior to fertilisation ; and (3) those which limit
sex-determination to no particular period, or which definitely
assert that sex may be established at different periods of
development in different animals.
(1) THEORIES WHICH ASSUME THAT SEX-DETERMINATION TAKES
PLACE SUBSEQUENTLY TO FERTILISATION
In tadpoles sex is apparently indeterminate until a rela-
tively late stage of development, but it is said to be established
at the time of metamorphosis. Born,3 and subsequently
1 Bodio, " Movimento della Populazione," Confronti Internazionali, 1895.
2 Punnett, "On the Proportion of the Sexes among the Todas," Proc.
Canib. Phil.Soc., vol. xii., 1904.
3 Born, " Experimentelle Untersuchungen ueber die Entstehung der
Geschlechtsunterschiede," Breslauer drztliche Zeit., 1881.
THE FACTORS WHICH DETERMINE SEX 625
Yung 1 and certain other investigators, have adduced evidence in
support of the view that the sex is determined by the quantity
and quality of the food supply. Thus they claimed that they
could produce an excess of females by feeding the tadpoles upori^
a meat or fish diet. The conclusions of these authors, however,
are hardly borne out by more recent researches, for Cuenot's
experiments,2 conducted on similar lines to those of Born and
Yung, show a preponderance of males among tadpoles which
were fed upon animal food, and an approximate numerical
equality among those which received an exclusively vegetable
diet. Moreover, the method adopted by Born for ascertaining
the sex of the individual tadpoles during the period of meta-
morphosis seems to have been unsatisfactory, since it was based
on the assumption that the ovary is always larger than the
testicle, whereas this is not invariably the case. It is stated
also that frogs' eggs from certain localities yield a higher per-
centage of females than those from other localities, and conse-
quently that a disproportion of the sexes may exist under normal
conditions, but this fact in itself does not show that sex is not
determined by nutritive or other environmental influences, but
may point to a directly opposite conclusion. But, as Morgan
points out, if the natural disproportion between the two sexes
is great, errors may easily creep into the experimental results.3
Lastly, King's observations relating to sex-determination in
Amphibians provide no evidence that either food or temperature
are factors in this process.4
The experiments of Treat 5 and other observers who at-
tempted to show that the sex of caterpillars could be determined
artificially by regulating the supply of food may be disregarded,
since it has since been shown that the sex in those animals
is already established at the time of hatching, while it is
1 Yung, "De 1'Influence de la Nature des Aliments sur la SexualiteY'
C. R. de VAcad. des Sciences., vol. xciii., 1881.
2 Cu^not, " Sur la Determination du Sexe chez les Animaux," Bull. Sci. de
France et Belg., vol. xxxii., 1899.
3 Morgan, loc. cit.
4 King, " Food as a Factor in the Determination of Sex in Amphibians,"
Biol. Bull., vol. xvi., 1909. "Temperature as a Factor," &c., Biol. Bull.,
vol. xviii., 1910.
5 Treat, " Controlling Sex in Butterflies," American Naturalist, vol.
vii., 1873.
2R
626 THE PHYSIOLOGY OF REPRODUCTION
improbable in the cases described that it could have been
reversed after having been differentiated. Furthermore, experi-
ments by Briggs 1 and other investigators have failed to support
the hypothesis that the proportion of the sexes can be altered by
modifying the diet, while Kellogg 2 has shown that in the case
of the silkworm moth, sex is definitely determined as early as
immediately after the first larval moulting, this conclusion being
based on an examination of the rudimentary reproductive glands.
According to Cuenot 3 the essential organs of reproduction
in the maggots of flies are not differentiated into ovaries or
testicles until a late period of larval development. There was
a possibility, therefore, that in these animals the sex could be
modified by the conditions of nutriment or other external
factors. Cuenot found, however, that the proportion of the
sexes was not materially affected by the supply of nourishment,
although the maggots were fed upon different kinds of food,
some being given brain, suet, and a little meat, some a large
supply of putrefying flesh, while others were relatively starved.
Among bees and other hymenopterous insects the nutriment
appears to be the main factor determining the difference be-
tween the two kinds of females (workers and queens). A
worker larva can be made to develop into a queen by supplying
" royal food/' that is, food which is given to young queens.
In the worker the female generative organs never fully develop,
but royal diet stimulates these organs to grow so that the larvae
become queens. A partially developed worker may be made
partially fertile by supplying it with some of the jelly obtained
from a royal cell. The following table shows the relative com-
position of the solid food given to workers and queens : 4—
Solid Food.
Workers.
Queens.
Nitrogenous .
Fatty ....
Glucose ....
51-21
6-84
27-65
45-14
13-55
20-39
This table shows that the quantity of fatty material supplied
1 Briggs, "Notes on the Influence of Food in Determining the Sexes of
Insects," Trans. Entom. Soc., London, vol. i., 1871.
2 Kellogg, " Notes on Insect Bionomics," Jour. ofExper. Zool., vol. i., 1904.
3 Cuenot, loc. cit. 4 Geddes and Thomson, loc. cit.
THE FACTORS WHICH DETERMINE SEX 627
to the developing queens is very nearly double that given to the
workers.
There is no evidence that drone larvae can be converted into
females by a supply of royal or other food, so that the case -oi
bees can scarcely be regarded as affording a real instance of sex
being determined by conditions of nutrition, since workers are
true females whose reproductive organs and other sexual char-
acteristics have failed to develop owing to an insufficiency of
stimulating food.
The case of white ants or termites is probably comparable,
though considerably more complicated, since the different kinds
of sexual individuals are more numerous. The young may
develop into workers, soldiers, or royal substitutes, and the
latter may be further transformed into fully fertile or " royal "
individuals, while both sexes (i.e. males and females) are
represented in each of these forms. Grassi's observations 1 point
strongly to the conclusion that these different kinds of indivi-
duals are developed from similar eggs under different condi-
tions of nutrition which is supplied to the young by the older
members of the community ; but here again there is no evidence
that males can be converted into females or females into
males.
Rolph 2 has described a series of observations on the pro-
duction of males and females in Nematus ventricosus, a species
of wasp. These observations show that the percentage of
females in broods of larvae reared from fertilised ova steadily
increased from June to August and then proceeded to diminish.
tc We may conclude without scruple, that the production of
females from fertilised ova increases with the temperature
and with the food supply (Assimilationsleistung), and de-
creases as these diminish." 3 Certain further experiments with
unfertilised ova of the same species seem to show that " the
more abundant the metabolism (Stoffwechsel) and the nutrition,
the greater the tendency to the production of females." In the
normal condition males only were produced as a result of
1 Grass! and Sandias, " The Condition and Development of the Society of
Termites," Quar. jour. Micr. Science, vols. xxxix. and xl., 1896-97.
2 Eolph, Biologische Problems, Leipzig, 1884.
3 Translated by Geddes and Thomson.
628 THE PHYSIOLOGY OF REPRODUCTION
parthenogenetic development, but the superior nutrition is
believed to have led to the production of females.
The fact that in certain Crustacea a condition of herma-
phroditism can be induced by an external cause acting on a
sexually differentiated individual is discussed below in dealing
with latent characters.
(2) THEORIES WHICH ASSUME THAT SEX-DETERMINATION TAKES
PLACE AT THE TIME OF FERTILISATION OR PREVIOUSLY TO
FERTILISATION
Effect of Fertilisation. — While it seems certain that queen
and worker bees are developed from fertilised eggs under
different conditions of nutrition, the conclusion is now fairly
established that drones or male bees arise parthenogenetically
from unfertilised eggs. If this view is correct, it clearly follows
that in bees the differentiation into female and male individuals
is brought about by the occurrence or non-occurrence of fertilisa-
tion. This theory of sex-determination in the bee was first
formulated by Dzierzon,1 and has since been accepted by
Weismann 2 and many other biologists, although some writers,
such as Beard,3 deny the conclusion that fertilisation is capable
of exercising any such influence.
In support of his contention Beard quotes an observation by
Weismann and Petrunkewitsch, showing that a drone egg may
occasionally undergo fertilisation. He also refers to the results
obtained by " bastardising " hives of bees through the intro-
duction of Italian queens into colonies of German workers and
drones, or of German queens into Italian swarms.4 In such a
bastard hive Dzierzon found a drone which appeared to be a
cross between a German and an Italian bee, and which conse-
quently afforded evidence of a drone egg having been fertilised.
This result led Dzierzon temporarily to doubt the truth of his
1 Dzierzon, " Uber die Befruchtung der Konigin," Eichstadt Bienen-
Zeitung, vol. i., 1845.
2 Weismann, " Ueber die Parthenogenese der Bienen," Anat. Anz., vol. v.
1900.
3 Beard, "The Determination of Sex in Animal Development," Zool.
Jahrb., vol. xvi., 1902.
4 Von Siebold, Wahre Parthenogenesis bei Schmetterlingen und Bienen,
Leipzig, 1856.
THE FACTORS WHICH DETERMINE SEX 629
hypothesis, but he subsequently accepted the interpretation of
von Siebold, who suggested that the queen which had given
rise to the apparently bastard drone was herself of impure
descent, and that in reality the egg had not been fertilised, _A_
further exceptional case has been recorded by Perez,1 who
found that a considerable number of male bees produced by an
Italian queen which had been fertilised by a French drone
appeared to be of mixed blood. This result, which is admittedly
unusual, has been explained by Sanson 2 as due to " reversion/'
while it has also been pointed out that the hybrid drones may
conceivably have arisen from hybrid workers which sometimes
lay eggs, and further that male bees are often very variable in
their characters.3 Either of these explanations would appear
to be possible.
Moreover, the later observations of Petrunkewitsch,4 showing
that sperm nuclei are not found in drone eggs whereas they
are commonly met with in worker eggs, supply an important
confirmation of Dzierzon's hypothesis.
Attempts to extend this hypothesis to other hymenopterous
insects have not been so satisfactory, though it seems, as a
general rule, to hold good for ants. There are instances on
record, however, in which worker ants have developed from
parthenogenetic ova, and other exceptional cases have been
stated to occur.5
Among the Tenthredinidae or sawflies also the unfertilised
eggs commonly develop into males, but this is by no means
invariable. Thus in some forms fertile parthenogenetic females
only have been known to arise for many generations in suc-
cession without the appearance of males.6
1 Perez, " Memoir e sur la Ponte de 1'Abeille reine et la Theorie de
Dzierzon," Annales des Sciences Nat., vol. v., 1878.
2 Sanson, "Note sur la Parthenogenese chez les Abeilles," Annales des
Sciences Nat., vol. v., 1878. 3 Morgan, loc. cit.
4 Petrunkewitsch, "Die Richtungskorper und ihr Schicksal im befruch-
teten und unbefruchteten Bienenei," Zool. Jahrb., vol. xiv., 1901. "Das
Schicksal der Richtungskorper im Drohnenei," Zool. Jahrb., vol. xvii., 1902.
5 Wheeler, " The Origin of Female and Worker Ants from the Eggs of
Parthenogenetic Workers," Science, vol. xviii., 1903.
6 Doncaster, " On the Maturation of the Unfertilised Egg and the Fate
of the Polar Bodies in the Tenihredinidoe" Quar. Jour. Micr. Science,
vol. xlix., 1906.
630 THE PHYSIOLOGY OF REPRODUCTION
In the parthenogenetic Rotifer, Hydatina, Maupas 1 has
adduced strong evidence that if the parthenogenetic male eggs
are fertilised they are thereby converted into " winter " eggs
which give rise solely to females. If this is so (and Maupas's
conclusions are now generally accepted), it is a clear instance
of fertilisation altering the sex of the individual. It is stated,
however, that impregnation has no effect unless it is performed
during the first few hours after hatching.
Certain writers have adopted the view that sex in animals
generally is regulated by the time at which fertilisation takes
place, that is to say, by the condition of the germ cells. Thus,
Thury 2 and subsequently Busing 3 expressed the opinion that
an egg which is fertilised shortly after ovulation usually de-
velops into a female, and that an older egg tends to produce a
male. Thury claimed that he could regulate the sexes in cattle
by allowing coitus only at the beginning or at the end of the
oestrous periods, an early coitus being supposed to result in
the birth of a female, and a late coitus in the production of
a male, but other investigators have failed to establish Thury 's
conclusions.
Influence of Nutrition. — Schenk 4 also has elaborated a highly
speculative theory which supposes sex to be determined by the
relative degree of " ripeness " or unripeness " of the ovum ;
but the term " unripeness " is here used to imply a condition
consequent upon incompleteness of nutrition, while " ripeness "
is held to result from a more favourable state of nutrition.
" Ripe " ova are supposed to develop into males, and " unripe "
ones into females. The presence of sugar in the urine is evidence
of an incomplete metabolism, and hence is regarded by Schenk
as implying a condition likely to result in the birth of females.
By supplying women with a highly nitrogenous diet, which
1 Maupas, "Sur la Multiplication et la Fecondation de 1'Hydatina
senta," C. R. de I'Acad. des Sci., vol. cxi., 1890. " Sur la Fecondation de
1'Hydatina senta," C. R. de VAcad. des Sci., vol. cxi., 1890. "Sur la
De"terminisme de la Sexualite chez Hydatina senta," C. R. de VAcad. des
Sci., vol. cxiii., 1891.
2 Thury, Ueber das Gesetz der Erzeugung der Geschlechter, Leipzig, 1863.
3 Diising, "Die Regulierung des Geschlechtsverhaltnissesbei der Vermeh-
rung," &c., Jenaische Zeitschr.> vol. xvii., 1884.
* Schenk, The Determination of Sex, English Translation, London,
1898.
THE FACTORS WHICH DETERMINE SEX 631
prevented the elimination of sugar in the urine and made the
metabolism more complete, Schenk claimed that he could ripen
the ova, and so increase the chances of male offspring.
Influence of Environment. — It has long been known that
parthenogenesis is the normal method of reproduction among ~
plant-lice or Aphides during the months of summer, successive
generations of individuals arising in this way, but that with the
approach of autumn males make their appearance and repro-
duction then becomes sexual. If, however, the Aphides be kept
in an environment of artificial warmth, and at the same time
are supplied with abundant food, the succession of partheno-
genetic females may be caused to continue for years without
the appearance of the sexual form. It is to be noted that the
sexual and parthenogenetic females are not identical, and also
that the same female may give rise to parthenogenetic and
sexual offspring, or to males and females, or to only one sex.
Moreover, Stevens has shown that male and female embryos
may be produced practically simultaneously by the same in-
dividual. It is maintained therefore by this writer that " the
changes in sex usually attributed to changes in external con-
ditions are really a change from the parthenogenetic to the
sexual mode of reproduction. The life cycle is often very com-
plicated, and in some species of Aphides there is evidence that
the environment (e.g. the trees on which they live) rather than
the temperature is responsible for the development of the sexual
forms.1
Many of the lower Crustacea undergo a somewhat similar
alternation of generations. For example, the water-flea
(Daphnia), after reproducing parthenogenetically during the
summer time, deposits eggs which give rise to sexual forms
at the commencement of autumn, and the female after impreg-
nation lays the winter eggs from which the new brood arises.
This result is generally supposed to be brought about by the
conditions of temperature or nutrition ; but Weismann,2 as a
consequence of numerous experiments and observations, has
1 Balbiani, " Le Phylloxera du Chene et le Phylloxera de la Vigne," &c.,
Mem. ct I'Acad. des Sri., vol. xxviii., 1884. Stevens, " Studies on the
Germ Cells of Aphids," Carnegie Institution Publications, Washington, 1906.
- Weismann, " Beitrage zur Naturgeschichte den Daphniden," Zeitsch.
f. wiss. Zoologie, vols. xxvii., xxviii., xxx., and xxxiii., 1876-79.
632 THE PHYSIOLOGY OF REPRODUCTION
cast doubts upon this view, believing rather that the animal
has been so constituted by natural selection that it tends spon-
taneously to reproduce sexually in the appropriate season, and
that it does so to a large degree irrespectively of the actually
existing conditions. More recently Issakowitsch l has carried
out an investigation upon another daphnid, Simocephalus,
from which he has been able to show that differences in tem-
perature may determine the mode of reproduction, but that
this result is effected indirectly by the change of temperature
altering the conditions of nutrition. Unfavourable conditions
tend to the production of sexual forms, and favourable ones to
the parthenogenetic method of generation. The same individual
female may give rise either to sexual or parthenogenetic offspring,
the conditions which exist in the ovary appearing to determine
what kind of egg will develop.
In the Rotifer Hydatina senta there are at least two kinds of
females, which are distinguished by the kinds of eggs that they
lay — (1) thelytokous females, which produce other females
parthenogenetically, and (2) arrenotokous females, which pro-
duce males parthenogenetically. The second kind of female
may also produce fertilised eggs. Furthermore, the thelyto-
kous females may give rise either to arrenotokous females or
to more thelytokous females, and the proportion of arreno-
tokous females so produced is liable to considerable variation.
Maupas 2 has sought to connect this variation with differences
in temperature, and Nussbaum 3 with differences in nutri-
tion, but neither conclusion has been satisfactorily established.
The question has been reinvestigated by Punnett,4 who has
carried out a number of further experiments. In one of these
a strain which had hitherto appeared to be purely thelytokous
was subjected to considerable fluctuations of temperature. The
rate of reproduction was much retarded, but in the subsequent
generations which were produced no arrenotokous females could
1 Issakowitsch, " Geschlechtsbestimmende Ursachen bei den Daphiden,"
Biol Centralbl, vol. xxv., 1905.
2 Maupas, loc. cit.
3 Nussbaum, "Die Entstehung des Geschlechtes bei Hydatina senta,''
Arch. f. Mikr. Anat., vol. xlix., 1897.
4 Punnett, "Sex-determination in Hydatina," Proc. Roy. Soc.t B.,
vol. Ixxviii., 1906.
THE FACTORS WHICH DETERMINE SEX 633
be found. Starvation experiments were undertaken, and in
these also thelytokous females which had hitherto " bred
true " continued to do so. Punnett concludes that neither
temperature nor nutrition has any influence in determining
the production of arrenotokous females. On the contrary, it
is the property of certain females to produce arrenotokous
females in a definite ratio, and the property of others to
produce none.
Theories which assume that the Gametes are themselves Sexual.
—Many biologists have entertained the conception that the
gametes are themselves sexual, and a number of facts have
been adduced which give very strong support to this idea. Some
of these have already been mentioned, but probably the
strongest evidence in favour of this generalisation is that relating
to the existence of sexually differentiated spermatozoa.
It has been known for a long time that two kinds of sperm
exist in the snail Paludina, a hair-like form and a worm-like
form, but it is commonly believed that only the former is func-
tional. Dimorphic spermatozoa have also been discovered in
various other animals, but the differences between the two
kinds vary greatly.1
Henking 2 made the discovery that in the bug, Pyrrhocoris,
half of the spermatozoa differ from the other half in possessing
an additional chromosome. McClung 3 was the first to suggest
that the difference between the two sorts of spermatozoa in this
insect was connected with sex-determination, and that those
which contained the accessory chromosome produced males and
that those without it produced females. The last assumption
has, however, proved to be incorrect, since Wilson 4 found that
1 A list of species in which dimorphic forms of spermatozoa have been
recorded (down to 1902) is given by Beard, loc. cit.
2 Henking, " Untersuchungen ueber die ersten Entwicklungsvorgange in
den Eien der Insekten," Zeitschr. f. wiss. Zool., vol. xlix., 1890, and vol. li.,
1891.
3 McClung, "The Accessory Chromosome Sex Determinant," Biol. Bull.,
vol. iii., 1902.
4 Wilson, " Studies on Chromosomes," Jour, of Exp. Zool., vols. ii. and
iii., 1905-6 ; vol. vi., 1909. " Note on the Chromosome Groups of Metapodius
and Banusa," Biol. Bull., vol. xii., 1907 ; "The Supernumerary Chromosomes
of Hemiptera," Science, vol. xxvi., 1907; see also Stevens, "Studies in
Spermatogenesis," Part I., 1905, and Part II., 1906, Carnegie Institution
634 THE PHYSIOLOGY OF REPRODUCTION
in this and other forms the female and not the male contains
an additional chromosome in its somatic cells. It is almost
certain also that the ova have one more chromosome than one
half of the sperms have, and the same number as that possessed
by the sperms which contain the additional chromosome.
Consequently the latter are supposed to produce females and
the former males.
For example, in Anasa tristis the somatic cells of the male
contain twenty-one chromosomes, whereas those of the female
contain twenty- two. Half of the spermatozoa are supposed to
contain eleven chromosomes, the other half having only ten.
The ova are believed to all resemble one another in containing
eleven chromosomes. It is concluded, therefore, that the
spermatozoa possessing the smaller number give rise to
males, while those with eleven chromosomes produce females.1
Payne 2 has recently shown that in Galgulus oculatus there
are two sorts of spermatozoa possessing respectively sixteen
and nineteen chromosomes, whereas the eggs are uniform in
containing nineteen chromosomes. Furthermore, the females
are believed to have three more chromosomes than the males
(i.e. thirty-eight as compared with thirty-five). It is evident
therefore that the sexual differences of the chromosomes, even
in the same order of animals, do not conform to a single
numerical rule, but at present it would appear that where there
is a difference in the number it is always the female which has
more chromosomes than the male.
That two sorts of spermatozoa (one with an additional
chromosome) may exist in other animals besides insects has
Publications, Washington. In these papers dimorphic spermatozoa (one kind
containing one smaller chromosome or lacking one chromosome) are described
for various species of Orthoptera, Coleoptera, Hemiptera and Lepidoptera.
1 Miss Foote and Strobell (" A Study of Chromosomes in the Spermato-
genesis of Anasa trislis" Amer. Jour, of Anat., vol. vii., 1907), as a result
of an investigation with smear preparations instead of sections, find no evidence
of a persisting accessory chromosome in Anasa trislis, and believe that the
body described as such by Wilson is a plasmosome and not a chromosome.
2 Payne, " On the Sexual Differences in the Chromosome Groups in
Galgulus oculatus," Biol. Bull., vol. xiv., 1908. Correns also has shown that
in some plants there are two classes of male germ cells, and that these are
produced in equal numbers (Die Bestimmung und Vererbung des Geschlechtcs
nach neuen Versuchen mit hoheren Pflanzen, Berlin, 1907).
THE FACTORS WHICH DETERMINE SEX 635
been shown by Guyer,1 who has investigated the matter for
the chicken and guinea-fowl.2 (See footnote 2, p. 657.)
The manner in which the spermatozoon with the accessory
chromosome (or chromosomes) produces a female is still an
open question. It is often supposed that the accessories are
themselves the carriers of those hereditary characters which
distinguish the female sex, but it may be that the result is due
simply to the greater amount of chromatin carried into the egg
in the process of fertilisation. " The result," as Morgan remarks,
" is similar to that of the bee, in the sense that the fertilised egg
contains more chromosomes than the unfertilised, and produces
in consequence the female.3 In the absence of all knowledge as
to how the greater quantity of chromatin produces a female, one
is tempted to assume that the result is reached through assimi-
lative changes that take place in the early cells, and there is some
evidence in favour of the view that one of the main functions of
the chromatin is to carry on the assimilative processes in the cells."
Morgan has shown further that in Phylloxera, in which all
the fertilised ova become females, the " male " spermatozoa
are rudimentary.4
The theory that there are two kinds of sexually differentiated
ova has also been advanced. In support of this contention it
has been pointed out that in Hydatina senta, Phylloxera, and
Dinophilus apatris, there are two sizes of eggs, and that in each
case the large eggs produce females and the small ones males.
It is not clear, however, whether the size determines the sex,
or the sex controls the size, but Beard says : " As the size of
the egg will naturally be attained during the oogenesis, it would
seem to follow, that here the destination of the oogonium must
1 Guyer, " The Spermatogenesis of the Domestic Chicken," Anat. Anz.,
vol. xxxiv., 1909 ; " Guinea-fowl," Anat. Anz., vol. xxxiv., 1909.
2 So also in the Nematode Heterakis and probably also in Ascaris (see
Boveri and Gulick, Arch. f. Zellforsch, vol. iv., 1909).
3 It is said that in the process of spermatogenesis in the drone one of the
maturation divisions is suppressed, a fact which suggests that only half the
normal number of chromosomes is present in the cells (Meves, Arch.f. Mikr.
Anat., vol. Ixx., 1907).
4 Morgan, "The Production of two Kinds of Spermatozoa in Phyl-
loxcrus," &c., Proc. Soc. Exp. Biol. and Med.t vol. v., 1908 ; " Sex De-
termination and Parthenogenesis in Phylloxera and Aphids," Science,
vol. xxix., 1909.
636 THE PHYSIOLOGY OF REPRODUCTION
be determined prior to the final phenomena of the reduction
and of the ripening, for these latter would not appear to possess
any influence on the size of the egg itself/' l Beard states that
the eggs of the skate, Raja batis, are likewise of two kinds. It
is also pointed out in support of Beard's view that according
to von Ihering 2 embryos which are found in one chorion (and
which are supposed, therefore, to have arisen from one ovum)
in the Edentate Praopus hybridus, are invariably of one sex,
and that " double monsters " in Man are of the same sex, while
Marchal 3 states that in the chalcid fly (Ageniaspis fuscicollis)
in which a chain of embryos takes origin from a single egg,
these embryos are all of one sex. (See footnote 2, p. 657.)
Beard asserts that sex is determined solely in the egg, and
that in those animals in which there are two kinds of spermatozoa
one kind is always functionless. This theory is clearly opposed
by the facts discovered by Wilson regarding the spermatozoa of
many insects, and by the case of the bee and other forms in which
sex is determined by fertilisation. It must be pointed out,
however, that, according to Morgan, in the parthenogenetic
Phylloxera, the egg has the power of determining sex by regu-
lating the number of its chromosomes in the same kind of
way as has been shown in the case of other insects for the
spermatozoon.4
The view has also been entertained that there is a relation
between the position of the ovary and the sex of the ova. Thus,
according to Rumley Dawson,5 the ova produced by the right
ovary become males, and those produced by the left become
females. This theory is believed to be applicable especially to
Man, and is based on clinical evidence and on a supposed alterna-
tion of the sexes of the eggs discharged at the ovulation periods.
It clearly cannot apply to birds, in which the left ovary only
is functional, and King6 has shown experimentally that it is
1 Beard, loc. cit.
2 Von Ihering, " Ueber Generations- wechsel bei Saugethieren," Biol.
Centralbl., vol. vi., 1886.
3 Marchal, "Kecherches sur la Biologie et le Developpement des
Hymenopteres parasites," Arch, de la Zool. Exper. et Gen., vol. ii., 1904.
4 Morgan, Proc. Soc. Exp. Biol. and Med., loc. cit.
5 Dawson, The Causation of Sex, London, 1909.
6 King, "Studies on Sex Determination in Amphibians," Biol. Bull.,
vol. xvi., 1909.
THE FACTORS WHICH DETERMINE SEX 637
inapplicable to Amphibians. The alternative theory that sex
depends on the position of the testis from which the fertilising
spermatozoon was derived has been negatived by Copeman 1 as
a result of an experimental investigation upon rats.
Castle's Theory. — Bateson 2 was the first to suggest that the
Mendelian laws are applicable to sex-heredity. This suggestion
has been elaborated by Castle 3 into a theory which is based on
the idea that sex is determined during the process of maturation,
when the male and female gametes are believed to undergo
differentiation. Thus, in the case of the ovum, the male or
female element is supposed to be ejected in one of the polar
bodies, while a similar process is thought to occur in spermato-
genesis, excepting that in the latter case all the products of
division become functional gametes. According to this hypo-
thesis the ordinary sexual individual is regarded as comparable
to a Mendelian hybrid. It is clear, however, that the ordinary
Mendelian interpretation requires modification if it is to be
applied to the phenomena of sex, since hermaphrodite in-
dividuals do not occur in accordance with the usual formula
which assumes a gametic segregation and three kinds of
conjugation according to the law of probabilities :—
Spermatozoa . 50 per cent, male + 50 per cent, female.
Ova . . 50 per cent, male + 50 per cent, female.
Result after \ ^ cent mm + 5Q cent ^ + ^
conjugation )
If this result actually happened, hermaphrodite individuals
(mf.) would be twice as common as individuals belonging to
either sex. Castle assumes, therefore, that male spermatozoa
are capable of conjugating with female ova only, and that
female spermatozoa can conjugate with male ova only. The
actual determination of sex in the zygote is supposed to
depend upon whether the male or female character is dominant.
Dominance, according to this theory, in dioecious forms, is
1 Copeman, " Sex Determination," Phys. Soc.} May, 1908.
2 Bateson, Report to the Evolution Committee of the Royal Society, I.,
1902.
3 Castle, " The Heredity of Sex," Bulletin of the Museum of Comparative
Zoology, Harvard, vol. xl., 1903.
638 THE PHYSIOLOGY OF REPRODUCTION
possessed sometimes by the male character and sometimes bv
j. j j
the female. No zygotic individual is of either sex purely, for
the characters of the recessive sex (whether it be male or female)
are latent, as has been shown both anatomically and experi-
mentally.1 In parthenogenetic animals, however, the female
character always dominates over the male whenever the
characters of both sexes are present together. In such species,
all the fertilised ova are female, those unfertilised ova which
are formed without the segregation of the sex characters are
also female, while male individuals only develop from un-
fertilised ova from which the female character has been
eliminated.
" The segregation of sex characters takes place in most
parthenogenetic animals, and doubtless in dioecious animals
also, at the second maturation division (the ' reduction
division ') of the egg, and probably at a corresponding stage
in spermatogenesis. For (1) eggs which develop without ferti-
lisation and without undergoing a second maturation divi-
sion contain both the male and female characters, the former
recessive, the latter dominant ; but (2) in normally partheno-
genetic species, eggs which, after undergoing a second matura-
tion division, develop without fertilisation, are always male
(except in the gall- wasp, Rhodites). In such species the female
character regularly passes into the second polar cell, the male
character remaining in the egg. In dioecious animals, on the
other hand, either sex character may remain in the egg after
maturation.'"
In Hydatina senta only a single division occurs in the matura-
tion of the male eggs, and this is held to be comparable to the
second maturation division of other parthenogenetic forms,
and in it a segregation of sex characters is believed to take
place. In the case of the female parthenogenetic ovum no
maturation division occurs. The parthenogenetic egg of the
gall-wasp (Rhodites roscc) undergoes two maturation divisions,
but apparently without segregation taking place in either of
them, for no reduction occurs (at least normally), the nucleus
of the ovarian egg, the three polar nuclei, and the nuclei of the
mature egg being alike in each containing nine chromosomes.
1 Evidence that this is so is given below (p. 652 et seq.).
THE FACTORS WHICH DETERMINE SEX 639
The offspring are almost invariably females. Castle concludes
that in those rare instances in which males are produced a
reduction of chromosomes probably takes place, the dominant
female character being then eliminated.
Experiments by Doncaster and Others. — Important evidence
has lately been obtained by Doncaster l as a result of breeding
experiments with certain Lepidoptera. He has shown that in
the moth Abraxas grossulariata, there is a rare variety, which
generally occurs only in the female sex. This variety, which
is called A. grossulariata lacticolor, is a Mendelian recessive,
so that when crossed with an ordinary grossulariata male, the
offspring are all typical, the lacticolor variety disappearing.
Experimental crossings yielded the following results :—
(1) Lact. 9 x gross. <$ gave males and females all gross.
(2) Heterozygous 2 9 x heterozygous £ gave gross. $ , gross.
9 , and lact. 9 .
(3) Lact. 9 x heterozygous £ gave all four possible forms
(gross. <£ ,lact. <$ , gross. 9 , and lact. 9 ),the lacticolor males
being the first ever seen.
(4) Heterozygous 9 x lact. $ gave gross. £ and lact. 9 •
(5) Lact. 9 x lact. $ gave lact. £ and lact. 9 •
(6) Wild gross. 9 x lacb. £ gave gross. $ and lact. 9 •
It is shown, therefore, that males of the lacticolor variety
can be produced by mating lacticolor females with heterozygous
males (i.e. with males obtained by crossing the two original
varieties, and so presumably bearing two sorts of gametes),
but that the converse mating (4) results in offspring which
are either grossulariata males or lacticolor females. Further-
more, whereas lacticolor females, mated with wild grossulariata
1 Doncaster, " Recent Work on Determination of Sex," British Associa-
tion Report, Dublin Meeting, 1908. See also Punnett and Bateson, "The
Heredity of Sex," Science, vol. xxvii. , 1908.
2 The term heterozygote has been given by Bateson to offspring result-
ing from the union of dissimilar gametes. Such organisms, according to
the Mendelian theory, produce more than one sort of gamete (see p. 194).
Homozygotes are formed by the union of similar gametes, and produce
gametes of one kind. Thus, homozygotes, as regards sex, are believed to
produce gametes bearing one sex character only (either male or female) ;
whereas heterozygotes, as regards sex, are supposed to give rise to both
male-bearing and female-bearing gametes.
640 THE PHYSIOLOGY OF REPRODUCTION
males (1) produce offspring which are of both sexes, but all of
the grossulariata variety, the converse cross (6) yields grossu-
lariata males and lacticolor females. It is concluded, therefore,
that the wild and presumably pure grossulariata females are
heterozygous for sex, femaleness being dominant and maleness
a homozygous recessive character. All the females are be-
lieved to produce male-bearing and female-bearing gametes in
equal numbers, whereas all the males appear to produce only
male-bearing spermatozoa. According to this view, in gameto-
genesis there is a repulsion between the female determinant and
the grossulariata determinant, so that each gamete can be the
bearer of one or other of these two characters, but not of both.
The results obtained by Miss Durham in her experiments
on cinnamon canaries are explicable on a similar hypothesis.
When a cinnamon male was mated with a green female, the
female offspring were cinnamon and the males green ; but
when a cinnamon female was paired with a green male, all the
offspring of both sexes were green.1 Where, however, a green
cock of the second generation (the T?1 generation produced by
crossing) was mated with a cinnamon hen, both green and
cinnamon birds of both sexes were produced ; but when a green
cock of the second (F^ generation was crossed with a green hen
the resulting male birds were all green, but the females were of
both types. A more complex case of a like kind has been
brought to light by Bateson and Punnett in their investigation
on the heredity of the black pigmentation of the silky fowl in
its crosses with brown Leghorns and other fowls with light
shanks. Here two allelomorphic characters, in addition to the
two sex determinants, are concerned, but Bateson and Punnett
state that the facts point very clearly to some such solution
as that indicated by Doncaster's experiments with Abraxas.
They suggest further that whereas in Vertebrates it is probable
that the female is heterozygous as regards sex (the production
of secondary male characters in castrated females supporting
this view), the work of Potts and Smith (see p. 308) on parasitic
castration in Crustacea points to the converse conclusion that
in these animals the male is heterozygous, assuming definite
1 Durham, Report to the Evolution Committee of the Royal Society, IV.,
London, 1908. Cf. p. 637.
THE FACTQRS WHICH DETERMINE SEX 641
female characters after the destruction of the testicles, while in
the female, castration merely arrests development.1
Ziegler s Theory. — Ziegler 2 has put forward a theory which
assumes that the chromosomes which are derived from a grand-
parental female tend to produce a female, and that those de-
rived from a grandparental male tend to give rise to a male.
Ziegler points out that the parental chromosomes as such cannot
determine the sex, since these are equal in number. He there-
fore assumes that the grandparental chromosomes are the
directing factor, and consequently that sex is a matter of chance
depending on the result of the reduction division during matura-
tion— that is to say, upon which member of a pair of homologous
chromosomes goes to one pole of the spindle and which to the
other. If the number of chromosomes derived from the male
grandparent is greatest, the sex will be male, and if the
chromosomes from the female grandparent are most numerous
the offspring will be a female. Ziegler 'a theory has been ad-
versely criticised by Morgan, who writes as follows : — " On Ziegler's
theory of sex it is evident that whenever the reduced number of
chromosomes is even, there may occur an exact balance of grand-
mother and grandfather chromosomes, hence the child can have
no sex at all. ... It seems improbable that the equal balance
of the maternal and paternal chromosomes could be counter-
balanced by the presence of chromosomes derived from the
grandparents, especially since these have also been contained in
one or the other parent whose sex, on the theory, should have in-
fluenced them to acquire the character of that parent. These and
other difficulties make Ziegler 's hypothesis very improbable/' 3
Heape's Views. — Heape 4 has recently expressed the belief
" that while each ovum and spermatozoon in the generative
glands contains within itself sex, which is probably determined
by the laws of heredity, the proportion of those male and
female ova and spermatozoa which are developed and set free
1 For further discussion see Bateson, Mendel's Principles, Cambridge,
1909.
2 Ziegler, Der Vererbungslehre in der Biologic, Jena, 1905.
3 Morgan, loc. cit. See also " Ziegler's Theory of Sex Determination
and an Alternative Point of View," Science, vol. xxii., 1905.
4 Heape, " Note on the Proportion of the Sexes in Dogs," Proc. Camb.
Phil. Soc., vol. xiv., 1907.
2s
642 THE PHYSIOLOGY OF REPRODUCTION
from the generative glands may be regulated by selective
action, exerted in accordance with the resultant of a variety of
extraneous forces. If this be true, the proportion of living
male and female ova and spermatozoa which are freed from the
generative glands, and the proportion of the sexes of the off-
spring which result therefrom, will thus be influenced/' A
similar suggestion had been made by Schultze l and also by
Morgan.2
Heape is of opinion, however, that just as there is evidence
that adult animals are never purely male or female,3 so it is
probable that the sexual products (i.e. the gametes) are them-
selves similarly constituted. According to this view, an ovum
or a spermatozoon may possess dominant male or female
characters as the case may be, and recessive characters of the
opposite sex. " In such cases the possibility of infinite grada-
tions of sexual differentiation in an individual would be vastly
increased, and from the point of view of heredity, such complex
conditions carry with them factors of the highest importance/'
Ova and spermatozoa in which the characters of one sex
are dominant are referred to as being male and female, and
Castle's conclusion is accepted, that an ovum of one sex must
always be fertilised by a spermatozoon of the opposite sex, but
whether the sex of the adult is determined by the ovum or by
the spermatozoon is a question which is left open, as it may
admit of a different answer for different species of animals, or
even for different individuals. Heape says, however, that even
if that be so, the sex of the ovum must be regarded as bearing a
regular relation to the sex of the embryo as surely as if it con-
ferred its own sex.
" On this assumption a female parent producing ova of one
sex only will give birth to embryos of one sex, unless the male
parent possesses no spermatozoa of the opposite sex wherewith
to fertilise it, in which case the union will be barren. Diising4
claimed that the statistical results he obtained from a study of
1 See below (p. 652 et seq.).
2 Morgan, loc. cit.
3 Cf. Castle (see above, p. 638). Evidence on this point, including some
of that adduced by Heape, is cited below in dealing with hermaphroditism
and the latency of sexual characters.
4 Diising, loc. cit.
THE FACTORS WHICH DETERMINE SEX 643
the mating of thoroughbred horses indicated the dominant
influence of the male parent on the sex of the offspring. Any
sire that usually produces spermatozoa of one sex only can be
fertile, as a rule, only with mares which produce ova of the other
sex, and to such an extent he determines the proportion of the
sexes of the offspring for which he is responsible ; but where the
sperm of both sexes is uniformly produced, the sire must be
fertile with all mares producing ova, and as only one ovum is
produced by each mare, the responsibility for the sex of the
offspring then lies solely with the female parent."
The opinion is expressed that much of the evidence cited to
show the dominating influence of the male parent on the off-
spring produced may be explained on this view ; " while
statistically the father might be shown to be responsible, physio-
logically the mother controls the governing influence."
It is assumed that in normal cases both sexes of ova and
spermatozoa are probably produced in the gonads in equal
quantities, and that in those females which shed all their ova
the proportion of the sexes in the offspring is, in all likelihood,
determined by Mendelian laws. But it is pointed out that in
many animals only a small proportion of the ova formed in the
ovary ever reach maturity, the remainder undergoing de-
generation and ultimately absorption (see p. 156). It is inferred,
therefore, that the proportion of the sexes among the ova which
survive and are discharged must depend directly upon the
causes which lead to the degeneration of some ovarian ova
and the continued development of others. On this view it is
held that the ova are subject to the same law of natural selection
as other organisms, and that in some cases the male ova are best
fitted to survive, and in other cases the female ones.
Heape l has shown further that in the ovary of the rabbit
two kinds of degeneration prevail, and that in one kind it is the
follicle which first begins to undergo atretic changes, and that
in the other kind it is the ovum that is earliest affected. The
former condition is regarded as evidence that the available
supply of nutriment is insufficient for the maintenance of all
the ova in the ovary, while the latter is interpreted to mean that
1 Heape, " Ovulation and Degeneration of Ova in the Rabbit," Proc. Roy.
Soc., B., vol. Ixxvi., 1905.
644 THE PHYSIOLOGY OF REPRODUCTION
the ovum, for one reason or another, is unable to assimilate
the nutriment provided for it. It is possible, therefore, that
nutrition may in this way exercise a selective action as regards
sex. In this connection it is interesting to note that, according
to Issakowitsch,1 the nutritive conditions prevailing in the
ovary of the daphnid Simocephalus are determinative as to
the kind of egg which will develop (i.e. whether it will be a
parthenogenetic or a winter " egg), and that the two kinds
of eggs are stated to arise in different parts of the ovary. More-
over, Heape suggests that the marked difference between the
death-rate of men and women during famines,2 for example,
may be reproduced among male and female ova in the ovary
when that organ is subjected to conditions of a homologous kind.
Heape 's general conclusions are summarised as follows :—
" (1) That through the medium of nutrition supplied to the
ovary, either by the quantity or by the quality of that nutrition,
either by its direct effect upon the ovarian ova or by its indirect
effect, a variation in the proportion of the sexes of the ova pro-
duced, and therefore of the young born, is effected in all animals
in which the ripening of the ovarian ova is subject to selective
action ;
" (2) That when no selective action occurs in the ovary the
proportion of the sexes of ovarian ova produced is governed by
laws of heredity."
Having arrived at these conclusions, Heape next adduces
evidence that certain external forces may affect the proportion
of the sexes in dogs. It is shown that amongst greyhounds
conception during the period from August to November is most
favourable to the production of males under the conditions of
breeding at present practised, and this result is attributed to
a selective action on the ova produced at this time. There
is evidence also that among dachshunds and Basset hounds
the seasons affect the proportions of the males and females
born. The bloodhound returns seem to show that an excessive
production of males is associated with inbreeding. Further,
there is statistical evidence that a higher proportion of males is
produced in the larger litters, that the larger dogs produce the
1 Issakowitsch, loc. cit.
2 Mclvor, Madras Census Reports, 1883.
THE FACTORS WHICH DETERMINE SEX 645
larger litters, and consequently that the larger breeds have a
racial tendency to produce an excess of dog pups. Lastly, the
schedule returns strongly support the popular belief that there
is a tendency to prolonged gestation when the embryo is of the.
male sex.
In a further paper l Heape discusses the apparent influence
of extraneous forces on the proportion of the sexes in two aviaries
of canaries, kept under different conditions. One aviary was
kept at a regular temperature during the breeding season ; it
was comparatively well lighted, and the sun had access to it.
On the other hand, the birds did not receive specially rich nutri-
tion. The other aviary was kept in a room facing north and
east, and the temperature was allowed to vary considerably
during the breeding time, but the birds were always fed with
a plentiful supply of rich food. In the former of the two cases
nesting, hatching, and moulting took place earlier, only about
half the percentage of loss was experienced, and from the nests
in which all the eggs were hatched, the percentage of males
produced was more than three times that which was obtained
from the other aviary, in which the environmental conditions
were less favourable. The results obtained in each case could
not be ascribed to the particular strains of canaries, since an
interchange of birds between the aviaries was not followed by
any material alteration in the proportion of the sexes in the
two environments. It is concluded, therefore, that the ova
were subject to a selective action on which depended the
proportional differences produced.
" As a rule in nature the climatic forces which stimulate
the activity of the generative functions are also associated with
a plentiful supply of food ; the conditions which excite the one
ensure the supply of the other. Among domesticated animals
living in the open air, on the other hand, any forcing of the
breeding time is brought about by special feeding. In neither
case are the results obtained comparable to those we have now
before us, where both the quality and the quantity of the food
supplied is regulated entirely independently of the other causes
1 Heape, " Note on the Influence of Extraneous Forces upon the Pro-
portion of the Sexes Produced by Canaries." Proc. Camb. Phil. Soc., vol. xiv.,
1907.
646 THE PHYSIOLOGY OF REPRODUCTION
which stimulate the activity of the generative system. It is
to this peculiar combination I attribute the regularity of the
remarkable differences shown in these aviaries."
In a still later paper 1 Heape shows that there is evidence
of the influence of extraneous forces upon the proportion of
the sexes produced by the white and coloured peoples of Cuba.
Illegitimate unions were found to give rise to a larger propor-
tion of females, and it is concluded that in this class of union
there is an exceptionally active metabolism of the mother
which favourably affects the development of those ovarian ova
which give rise to female offspring.
Heape suggests further that much of the evidence that has
been collected in regard to the influence of nutrition and other
environmental causes upon the proportions of the sexes, although
it may be disregarded from the point of view from which it was
put forward (since it is commonly assumed that the conditions
directly determine the sex of the embryo), may yet be well
worthy of attention from the standpoint adopted by him.
Some of this evidence is briefly referred to below.
(3) THEORIES WHICH LIMIT SEX-DETERMINATION TO NO
PARTICULAR PERIOD OF DEVELOPMENT, OR WHICH ASSERT
THAT SEX MAY BE ESTABLISHED AT DIFFERENT PERIODS.
Influence of Age of Parent. — Hofacker 2 and Sadler 3 arrived
independently at the conclusion that the sex of the offspring
depends on the relative ages of the parents — that when the
father is the oldest more male births occur, and similarly when
the mother is the oldest there tends to be a preponderance of
females. This hypothesis, which is known as Hofacker and
Sadler's Law, has been both confirmed and contradicted,4 but
the most recent statistical investigation 5 on the causes con-
1 Heape, " The Proportion of the Sexes Produced by Whites and
Coloured Peoples in Cuba," Phil. Trans., B., vol. cc., 1909.
2 Hofacker, Ueber die Eigenschaften welche sich bei Menschen und
Thieren aufdie Nachkommen vererben, Tubingen, 1828.
3 Sadler, The Law of Population, London, 1830.
4 Geddes and Thomson, loc. cit.
5 Newcomb, " A Statistical Inquiry into the Probability of Causes of the
Production of Sex in Human Offspring," Carnegie Institution Publications,
THE FACTORS WHICH DETERMINE SEX 647
trolling sex in Man lends no support to it. Moreover, Schultze 's
experimental investigation *• on the sexes produced by mice of
different ages has led likewise to a negative result.2
Influence of Parental Vigour or Superiority. — Considerable
importance has been attached by breeders and others, and
notably by Starkweather,3 to the comparative vigour or con-
dition of the parents as a factor in sex determination. Ac-
cording to Starkweather, the superior parent tends to produce
the opposite sex. This theory has been accepted by Allison,4
who believes it to be applicable to thoroughbred horses. It
is obvious, however, that in attempting to apply Starkweather's
hypothesis much depends on the signification to be attached
to the term " superiority," and for this, if for no other reason,
the theory is unsatisfactory. Furthermore, Schultze 5 has
shown that long-continued or strained reproduction in female
mice has no effect on the proportion of the sexes produced.
The results of experiments on the effects of inbreeding were also
indefinite or contradictory.
Influence of Nourishment. — Of the various external factors
which have been supposed to have direct, influence in determin-
ing sex, nourishment seems to have found more favour than
any other. In some cases this factor is supposed to act upon
the developing embryo or larva (see p. 624), and so to determine
its sex, while in other cases it is concluded that sex is established
at an earlier period.
Geddes and Thomson have elaborated the idea that favour-
able nutritive conditions tend towards the production of females,
and unfavourable ones towards the development of males, and
certain of the evidence referred to above (p. 624) has been cited
Washington, 1904. Newcomb states that the first-born child of any mother
is more likely to be a boy in the proportion of about eight to seven.
1 Schultze, "Zur Frage von den geschlechts-bildenden Ursachen," Arch,
f. Mikr. Anat., vol. Ixiii., 1903.
2 This theory, and that which follows, should possibly be included among
those which assume that sex is settled at fertilisation ; for if sex is determined
by the age of the parents, it seems to follow that no event occurring during
embryonic life can alter it. This point, however, does not appear to have
been raised by the authors of the theory.
3 Starkweather, The Law of Sex, London, 1883.
4 Allison, The British Thoroughbred Horse, London, 1901.
5 Schultze, loc. cit.
648 THE PHYSIOLOGY OF REPRODUCTION
by them in support of this hypothesis. The normal female
metabolism is said to be relatively anabolic, while the greater
activity of the male is held to indicate a preponderance of kata-
bolic conditions. Consequently the generalisation is reached
that abundant or rich nutrition (or any other favourable circum-
stance) tends to induce an anabolic habit, and so favours the
development of females ; and conversely, that deficiency of the
necessary food supply (or any adverse circumstance) leads to a
katabolic condition of life, and so causes the production of males.
According to this idea, the organism is at first " sexually in-
different," the sex becoming established at varying periods of
development in different animals according to the circumstances.
Thomson has recently admitted that some of the evidence
which was formerly adduced in support of this view has since
been invalidated, and that it seems being proved more and
more that sex is fixed in the fertilised ovum or earlier, and
consequently that subsequent conditions of nutrition can play
no part in determining the relative proportion of males and
females. But Thomson is still disposed to lay stress on the
connection between sex and metabolism, believing that the
determinants for each of the sexual characteristics (both male
and female) are present in all ova and in all sperms, and that
their liberation or latency depends on a bias towards egg-
production or sperm - production. The so-called contrasted
peculiarities of the two sexes are due in certain cases " to in-
ternal physiological conditions which give the same primordium
two different expressions, much less different than they seem."
Statistics of human births have been brought forward in
support of the view that the proportion of the sexes varies with
the conditions of nutrition. It has been pointed out that in
France the proportion of births of boys and girls is 104-5 to 100
for the upper classes (which are presumably best nourished)
and 115 to 100 for the lower classes (who are more poorly fed).
In the Almanack of Gotha the proportion recorded is 105 boys
to 100 girls, while for Russian peasants this proportion is 114 to
100. Among the nobility of Sweden statistics show a proportion
of 98 male to 100 female births, but that given for the Swedish
clergy is 108'6 boys to 100 girls.2 There is therefore some
1 Thomson, Heredity, London, 1908. 2 See Morgan, loc. cit.
THE FACTORS WHICH DETERMINE SEX 649
slight evidence that the percentage of female births is a little
higher among those classes which are best nourished or subject
to more favourable circumstances, but the differences are very
small.
Punnett 1 has examined the statistics collected in the official
census of the county of London for the year 1901, with a view
to determining the relative proportions of the sexes amongst
different classes of society. The following is his summary and
conclusion : —
" If the population of London be divided into three portions
exhibiting graduated poverty, it is found that the proportion of
male to female infants produced [or rather which have sur-
vived] is lowest in the poorest portion, highest in the wealthiest
portion, and intermediate in the intermediate portion. The
proportion of males is highest of all in a number of births taken
from Burke 's Peerage, where the nutrition may be supposed to
be of the best. From this alternative conclusions may be
drawn : that either more favourable conditions of nutrition
(1) may result in a large proportion of male births [a conclusion
which is contrary to that indicated in the returns mentioned
above, but which nevertheless appears to be warranted at first
sight], or (2) may have no effect on the proportion of the sexes,
or (3) may even result in a relative preponderance of female
births, but that in the last two cases the effect is masked by
other factors which affect unequally the different strata of
society. Such factors are shown to exist in a differential infant
mortality, a differential birth-rate, and probably also in a
differential marriage-age. These factors all tend to diminish
the proportion of males in the poorer portions of the population,
and consequently render the first of the above alternative con-
clusions improbable. Whether the second or third of the other
possible conclusions is to be accepted must remain doubtful so
long as we are not in a position to estimate the quantitative
effect of the factors given above. From the necessarily rough
estimate which he has been able to form, the writer's opinion is
that their combined effect would not be sufficiently great to
mask a preponderance of female births due to better nutrition,
1 Punnett, " On Nutrition and Sex-Determination in Man," Proc. Camb.
Phil. Soc., vol. xii., 1903.
650 THE PHYSIOLOGY OF REPRODUCTION
and consequently he is inclined to believe that in man, at
any rate, the determination of sex is independent of parental
nutrition. In any case its influence can be but small. "
Cuenot's experiments l upon rats, in which some were fed
mainly on bread and others were fed upon an abundant supply
of different kinds of food, yielded no evidence of a preponderance
of one sex among the better-nourished individuals.
Lastly, in Schultze 's experiments 2 on mice, in which one
lot was starved and other lots were variously nourished upon
different kinds of foods, there is no evidence that sex-determina-
tion is regulated by nutrition.
Schultze and Morgan conclude that if nutrition really in-
fluences the proportion of the sexes, it is probable that it does
so indirectly by eliminating one or the other kind of egg. This
suggestion has been further elaborated by Heape, as described
above (p. 641).
Newcomb's Statistical Investigation. — Newcomb,3 as a result
of an investigation into the statistics of multiple births, has
come to the conclusion that sex is established at different periods
of development in different cases. He shows that there is a
tendency among human offspring for twins to be of the same
sex, a fact which he regards as supplying a " practically con-
clusive negation of the theory of completely determined sex in
the original germs." His conclusion appears to be that sex
is established by " accidental causes," the nature of which is
at present unknown, and that in the case of twins the sex-
determining factors act similarly on both children, and so tend
towards a uniformity of sex. But he omits to mention the
probability that some twin embryos arise from a single ovum,
a fact which would account for their sexual identity on the
assumption that sex is already .determined in the germ cell.
HERMAPHRODITISM AND SEXUAL LATENCY
Organisms which combine within themselves the essential
characters of both sexes are said to be hermaphrodite. True
hermaphrodites produce both ova and spermatozoa, but there
1 Cuenot, loc. cit. 2 Schultze, loc. cit.
3 Newcomb, loc. cit.
THE FACTORS WHICH DETERMINE SEX 651
are all gradations between true and partial hermaphroditism
(in which the essential organs of reproduction are not involved),
and between the latter and the completely unisexual condition,
in which the characters of the other sex are either latent or^
absent altogether.
Complete hermaphroditism is the normal state in many
groups of invertebrate animals (many sponges, ccelenterates, and
worms, and some molluscs and crustaceans). In some forms the
male and female sexual elements do not exist contemporaneously,
but are called forth separately by different environmental con-
ditions or are associated with particular phases in the repro-
ductive cycle (see Chapter I.). In such cases the fact that the
animal is hermaphrodite is liable to be obscured.
Among vertebrate animals true hermaphroditism is rare,
though its casual occurrence has been recorded even in
Mammalia, and is said to be comparatively frequent in
certain species of Amphibia.1
According to Castle 2 the true hermaphrodite is a sex mosaic,
the alternative sexual characters existing side by side without
dominance of either, and passing (without segregation) into the
gametes. Dioecious individuals are supposed to result ordinarily
from a union of gametes in which one sex is dominant and the
other recessive, so that no one individual is purely either male or
female. The occurrence of partial hermaphroditism may be
held to be an expression of an incomplete dominance of the
characters of one sex.
Partial hermaphroditism is usually said to occur when only
one kind of gonad is developed (either testis or ovary) in
conjunction with accessory generative organs characteristic of
1 See Geddes and Thomson, loc. cit. Curtis, " Studies on the Physiology
of Reproduction in the Domestic Fowl " (Biol. Bull., vol. xvii., 1909). Pearl
and Surface have described a case of an hermaphrodite fowl which had a
testis on one side and an ovary on the other. The accessory organs were
likewise unilaterally arranged. Externally it was an antero-posterior
gynandromorph, having male characters in front but female body characters.
Cf. Weber's finch (p. 313), which was a lateral gynandromorph. Such
gynandromorphs are not uncommon among some insects (Hymenoptera).
See also Shattock and Seligmann's papers quoted on p. 315. For an
exhaustive account of the question of hermaphroditism in Man, with a
full discussion of the evidence, see von Neugebaur, Hermaphroditismus
beim Menschen, Leipzig, 1908. 2 Castle, loc. cit.
652 THE PHYSIOLOGY OF REPRODUCTION
both sexes. Such cases are by no means uncommon even among
the higher animals. The so-called " Free-Martins " among
cattle have been held to be examples of incomplete herma-
phroditism. According to Berry Hart, however, the Free-
Martin is in reality a sterile bull which is co-twin of a normal
fertile bull.1
Among animals which are usually regarded as purely
dioecious there are many instances of vestigial or even of func-
tional sexual organs characteristic of one sex being present
normally in individuals of the opposite sex. The mammary
glands and teats of the male mammal, and the clitoris of the
female are examples of such organs. A more striking case is
that of the pipe fish (Siphostoma floridce), in which the male
possesses a marsupium which acts functionally as a placenta.2
Such cases as these have led Castle, Heape, and others to
conclude that all animals and plants are potentially herma-
phrodite, inasmuch as they contain the characters of both
sexes, although ordinarily the characters of one sex only are
developed, while those of the other are either latent or im-
perfectly developed.
Castle has cited cases from among plants in which the
characters of one sex can be induced to appear by the artificial
destruction of those of the other. Examples of the same kind of
1 Berry Hart, " The Structure of the Reproductive Organs of the Free-
Martin, with a Theory of the Significance of the Abnormality," Proc. Roy.
Soc. Edin., vol. xxx., 1910. The Free-Martin has also been regarded as a
sterile cow born co-twin with a potent bull. In most cases a vagina and
rudimentary uterus have been described, but vesiculse seminales and other
male organs are also stated commonly to occur. Berry Hart bases his
explanation of the occurrence of Free-Martins upon his recently elaborated
theory of sex. (Mendelian Action on Differentiated Sex, Edinburgh, 1909.)
According to this theory, sex is determined by a "sex-gamete" which
may be either male or female. There are also male and female "non-
sex gametes," which unite with the "sex-gametes" but are non-potent
in determining sex. A female sex-gamete uniting with a male non-sex
gamete gives rise to a female zygote, and conversely. Moreover, according
to Hart, a Free- Martin with a potent bull twin is the result of a division
of a male zygote, so that the somatic determinants are equally divided,
but the gametic determinants unequally divided, the potent going to the
one twin, the potent bull, and the non-potent to the Free-Martin.
2 Gudger, " The Breeding Habits and the Segmentation of the Egg of
the Pipe-Fish, Siphostoma Florida," Proc. U. S. Nat. Mus., vol. xxix.,
1905.
THE FACTORS WHICH DETERMINE SEX 653
phenomenon are supplied by certain animals. Thus Potts 1 has
shown that in the male Hermit Crab ova make their appearance
in the testes, and the secondary sexual characters become modi-
fied in the direction of the female as a consequence of the animal
being affected by the parasite Peltogaster. Similar changes
occur in a number of other animals belonging to widely different
groups, but they are especially common in the Crustacea.
Smith, who has paid considerable attention to this subject,2
explains the phenomenon by assuming that the males, in order to
cope with the drain on the system caused by the parasites, have
to increase their vegetative activity, and that they do this by
suppressing their male organisations and calling into play the
female ones, which they possess in a latent condition. In
further support of this view, Orton has shown that in the mollusc
Crepidula fornioata also the males under certain conditions may
change into females, thus showing that they have the poten-
tialities of both sexes.3
Further evidence in support of the view that each sex is latent
in the other is afforded by the well-known fact that the characters
of one sex can be transmitted through the other. For example,
Darwin states that the gamecock can transmit his superiority
in courage and vigour through his female offspring to his male
grandchildren, while with Man it is believed that diseases such
as hydrocele, which are necessarily restricted to the male sex,
can be handed on through female children to a future generation.4
Again, it is well known to cattle-breeders that a bull which is
descended from a good milking stock can transmit this quality
to his female offspring.
Smith has laid much stress on the relation between sex and
metabolism, inasmuch as changes in the latter are capable under
certain circumstances of calling forth the characters of the
1 Potts, " The Modification of the Sexual Characters of the Hermit Crab
caused by the Parasite Peltogaster," Quar. Jour. Micr. Science, vol. 1.
1906. (See p. 308, Chapter IX.)
2 Smith (G.), "Sex in the Crustacea," &c., British Association Report,
Leicester Meeting, 1907; "Studies in the Experimental Analysis of Sex,"
Quar. Jour. Micr. Science, vols. liv. and lv., 1910. (See p. 658.)
3 Orton, "On the Occurrence of Protandric Hermaphroditism in the
Mollusc Crepidula fornicata," Proc. Roy. Soc., B., vol. Ixxxi., 1909.
4 Darwin, The Variation of Animals and Plants, vol. ii., Popular Edition,
London, 1905.
654 THE PHYSIOLOGY OF REPRODUCTION
opposite sex. In this connection it is important to note that
the removal of the testes in the male is believed in certain
instances to lead to the development of the secondary female
characters, and that conversely the extirpation of the ovaries
in the female is said sometimes to cause the assumption of the
male characters (see p. 314). Moreover, Darwin and others have
shown that female birds (e.g. poultry, pheasants, ducks) in old
age, when the ovaries are no longer functional, or in cases where
these organs are diseased or have been injured by shot, some-
times acquire the secondary sexual characters of the male. So
also Wallace l states that aged mares tend to assume the arched
neck characteristic of the stallion. Conversely, cases are re-
corded in which characters and habits ordinarily confined to the
female are assumed by the castrated male. Thus Darwin states
that capons have been known to incubate eggs and bring up
chickens, and that sterile male hybrids between the pheasant
and the fowl may act in a similar manner. Such cases as
these are evidence of the latency of characters belonging to the
recessive sex in individuals of the other sex. Furthermore,
in studying the sexual pathology of youth and old age, there
are a number of well-ascertained facts that point in a similar
direction.
Weininger 2 has elaborated the idea that just as there may
be an " Idioplasm " that is the bearer of the specific characters
and exists in all the cells of a multicellular animal, so also
there may be two sexual modes in which this idioplasm can
appear, namely an " Arrhenoplasm " or male plasm, and a
" Thelyplasm " or female plasm. He maintains further that
every metazoon cell (and not merely every reproductive cell)
has a sexuality lying somewhere between arrhenoplasm and
thelyplasm, but that the actual degree of maleness or femaleness
varies in the different groups of cells of which the animal is
built up. Moreover, the different parts of the organism are
supposed to possess their own sexual determinants, which are
believed to be stable from their earliest embryonic foundation.
Weininger makes no suggestion as to what it is that determines
1 Wallace, Farm Live-Stock of Great Britain, 4th Edition, Edinburgh
1907.
2 Weininger, Sex and Character, English Translation, London, 1906.
THE FACTORS WHICH DETERMINE SEX 655
the differentiation of the original protoplasm into arrhenoplasm
and thelyplasm, but his idea, though somewhat too morpholo-
gically conceived, is useful if only because it emphasises the
fact that male and female characters coexist (though they are
very unequally represented) in most if not in all dioecious in-
dividuals— that is to say, that such individuals are rarely, if
ever, wholly male or wholly female. ' There may be conceived,"
he tells us, " for every cell all conditions, from complete
masculinity through stages of diminishing masculinity to its
complete absence and the consequent presence of uniform
femininity/*
Weininger draws special attention to the gradations in
sexual characters which exist among men and women. There
are many men, he remarks, with a poor growth of beard and
a weak muscular development, who are otherwise typically
males ; and so also there are women with ill-developed breasts
who in other respects are typical females. There exist all
transitional forms from the most masculine male to the most
effeminate male, and on the other side, from the Sapphist and the
virago to the most feminine female ; but in Man the characters
of one sex are always dominant, though the degree of dominance
varies through considerable limits. On this view, the phenomena
of so-called sexual inversion and homosexuality, which are
ordinarily regarded as purely pathological, are in reality psycho-
logical manifestations of special characters belonging to the
recessive sex.1
It is usual to regard the sex of an animal as being contributed
by the essential reproductive organs, while the effect of re-
moving these organs points to the conclusion that they exercise
by means of their internal secretions a very powerful influence
over the entire organism and more particularly over those char-
acters the development of which is ordinarily correlated with
1 For further information see Krafft-Ebing, Psycliopathia Sexualis,
Stuttgart, 1882 ; Havelock Ellis, Studies in the Psychology of Sex : Sexual
Inversion, Philadelphia, 1901 ; Forel, The Sexual Question, English Transla-
tion, London, 1908 ; and Bloch, The Sexual Life of our Tim°, English
Translation, London, 1908. For a discussion on the distinctions between
men and women, see Manouvrier, " Conclusions generates sur 1'Anthropologie
des Sexes et Applications sociales," Rev. de VEcole d1 Anthropologie de Paris,
1909.
656 THE PHYSIOLOGY OF REPRODUCTION
sexual potency. But it has been shown that castration, while
tending in certain cases to favour the development of characters
belonging to the opposite sex, results frequently in a distinctive
sexual type, as the experiments of Sellheim and others have
shown. Moreover, in certain forms of life (e.g. insects) the
secondary sexual characters are developed independently of
the essential organs of reproduction (see p. 307), the sexual
characteristics of the different tissues, although clearly correlated
to a large extent in most individuals, being independent of one
another when once they have been laid down in embryonic life.
This fact is demonstrated by Crampton's experiment in grafting
the heads of caterpillars from individuals of one sex on to those
of the other sex.
It would appear possible, therefore, that in exceptional in-
dividuals, whose sex has been assigned to them on account of
the presence of testicles or ovaries, the sexual complement is to
be found actually on their own side of the sexual line — that is
to say, on the side on which they are reckoned, although in
reality they may belong to the other.1 In the terms of
Weininger's hypothesis, such individuals would be regarded as
possessing more arrhenoplasm than thelyplasm (or conversely),
although the particular kind of plasma that predominates in
the soma is unrepresented in the organs of generation.
Lastly, Weininger's theory helps to explain why it is that
transplantation of gonads on animals of the opposite sex is
usually attended by failure, a fact which has been noted by
Ribbert and others, including the present writer. The internal
secretions of the ovaries or testicles, on this view, are operative
only in an appropriate environment of thelyplasm or arrheno-
plasm, or, to speak physiologically, in the existence of a re-
sponsive metabolism, and without this their influence on the
organism is ineffective, even though they succeed in becoming
attached.
In criticism of Weininger's morphological hypothesis, it
must be pointed out again that there is no real evidence that
any sort of character, whether sexual or otherwise, is at any
time definitely located in a special kind of material or plasma
(not even in the accessory chromosome, since this probably
1 Weininger, loc. cit.
THE FACTORS WHICH DETERMINE SEX 657
is merely one factor in a complex system of causes), and that
the physiological mode of thought requires one to associate the
characters of an organism with its particular metabolism and
not with any special sort of cell substance.1
GENERAL CONCLUSIONS
If it be true that all individuals are potentially bisexual
(one of the two sexes being recessive or latent excepting in
hermaphrodites), and that changed circumstances, leading to a
changed metabolism, may, in exceptional cases, even in adult
life, cause the development of the recessive characteristics (as
in the case of the Crustaceans mentioned above), it would seem
extremely probable that the dominance of one set of sexual
characters over the other may be determined in some cases at
an early stage of development in response to a stimulus which
may be either internal or external. The observations which
Smith and others have made upon certain Crustaceans point
even to the possibility that sex may be reversed after it has
once been established.
It seems certain that sex is not determined by the same
factors in all cases, neither is it determined at the same period
of development. It may well be that some gametes have an
initial tendency to give rise to males and others to give rise to
females, and to this extent it is probably legitimate to speak
of male and female ova or male and female spermatozoa.2 More-
over, the conclusion is probably correct that these are developed
(at least generally) in simple Mendelian ratios. But it is also
probable that no gamete is either purely male or purely female,
and it is possible that in some the two kinds of sexual determi-
nants or tendencies are about equally represented.
1 The presence of a certain kind of cell substance must of course influence
the metabolism, but the extent of its influence will depend upon other factors,
and may vary with different external conditions.
2 Bateson and Punnett suggest that in some forms of life (e.g. Verte-
brates) the ova are the sexually differentiated gametes, and that in other
organisms (e.g. Crustaceans) the sexual differentiation occurs among the
spermatozoa. Guyer's cytological observations, however (p. 635), seem to
show that male Vertebrates may be sexually heterozygous. Moreover,
Baltzer's cytological observations seem to show that among sea-urchins there
may be two kinds of eggs (Arch. f. Zellforsch., vol. iv., 1909).
2T
658 THE PHYSIOLOGY OF REPRODUCTION
When once we admit the existence of latent (i.e. recessive)
sexual characters in individuals in which the characters of one
sex are dominant, and that under certain circumstances those
of the latent sex can develop at the expense of the dominant ones,
in response to appropriate physiological stimuli, we are compelled
to acknowledge also that the sex of the future individual is
not always predetermined in the gametes or even in the fertilised
ovum, but may be called into being at a later stage of life.
Such an admission is of course opposed to some extent to
the modern tendency to believe that sex is fixed irrevocably in
the fertilised ovum or in the gametes before fertilisation ; but
while there is evidence amounting to proof that this is the case
in some forms of life, it does not necessarily follow that it is true
of all metazoon animals, or even that it is uniformly so of the
particular species which have been investigated. On the other
hand, many of the facts enumerated above point to the con-
clusion that the sex of the future organism is determined in
different cases by different factors and at different stages of
development — either in the unfertilised gamete, or at the
moment of fertilisation, or in the early embryo, while the effects
of castration indicate that an alteration in the metabolism, even
in comparatively late life, may initiate changes in the direction
of the opposite sex.1
APPENDIX
Braem 2 has described an experiment in which he divided in half a
mature female of the annelid, Ophryotrocha puerilis. The head portion
after some weeks regenerated and produced spermatozoa, but the ova
almost disappeared. There was no sign of hermaphroditism at the
outset, and Braem regards the case as one of change of sex resulting from
altered conditions.
In a recent paper Potts 3 has adduced evidence that in certain
hermaphrodite Nematodes, in Rhabdocoel Turbellarians and in Eliizo-
cephala the monoecious condition has arisen through the sperms
developing in the ovaries in gradually increasing numbers in successive
generations.
Smith 4 states that in the male of Inachus affected by Sacculina the
assumption of adult female characters is due to the formation of a yolk
substance (or female generative substance) similar to that normally
elaborated in the ovaries.
1 Such changes are notoriously more difficult to effect after puberty than
before it. 2 Braem, Anat. Anz., vol. xxxiii., 1908.
3 Potts, Quar. Jour. Micr. Science, vol. lv., 1910.
4 Smith, Quar. Jour. Micr. Science, vol. lv., 1910.
CHAPTER XVI
PHASES IN THE LIFE OF THE INDIVIDUAL— THE
DURATION OF LIFE AND THE CAUSE OF DEATH
"TavTbv yap i7/3aW tivSpa KCU Trpe<r/3vv Oaveiv;" — EURIPIDES, Alcestis.
THE physiological life of the metazoon individual begins with the
union of sperm and ovum, and the organism thus formed thence-
forth proceeds to grow. As has been said by Verworn,1 there
is an essential similarity between reproduction and growth,
both processes consisting of an increase of living substance.
" The difference between that which is usually termed growth
in the narrow sense and the phenomenon of reproduction consists
only in the fact that in the former case the newly-formed living
substance remains in constant connection with the original
organism and helps to increase its volume ; while in the latter
case a part of the substance separates itself from the original
organism, either, as in most cases, being set entirely free, or, as
in the increase of tissue-cells, being separated merely by a
partition-wall and remaining in place/' Among the more
highly organised Protozoa there are various transitional stages
between these two conditions.
Growth, like reproduction, involves cell division. As the
mass of living substance increases, the cells must multiply, for
every cell has assigned to it a limit in size beyond which it
cannot pass. Cell division goes on, though with gradually
decreasing frequency throughout practically the whole of life ;
tissue formation continues, but from an early period of de-
velopment onwards there is a progressive diminution in the
power of growth. Increase in the number of cells is, how-
ever, specially characteristic of the embryonic period. In the
later stages of development growth occurs largely through cell
enlargement and the deposition of intercellular substance.
1 Verworn, General Physiology, Lee's Translation, London, 1899.
659
660 THE PHYSIOLOGY OF REPRODUCTION
Minot has compared the growth of the body to a man building
a wall.1 " He begins at first with great energy, full of vigour ;
the wall goes up rapidly ; and as the labour continues, fatigue
comes into play. Moreover, the wall grows higher, and it
takes more effort and time to carry the material up to the top
of the wall, and to continue to raise its height, and so, as the
wall grows higher and higher, it grows more slowly and ever
more slowly, because the obstacles to be overcome have in-
creased with the very height of the wall itself. So it seems with
the increase of the organism, and with the increase of our
development, the obstacles to our growth increase." According
to Minot, the explanation of this phenomenon must be sought
in the differentiation of the protoplasm, which goes on growing
with an ever-increasing complexity as the cells of the body
multiply.
It has just been mentioned that every cell has assigned to
it a definite limit in size beyond which it cannot go. Boveri 2
has enunciated the general law that the process of cell division
is regulated by the proportion of chromatin material to cyto-
plasm, and that it comes to a standstill when the ratio of the
mass of chromosomes to that of the cells in any given tissue or
organ reaches a certain definite point. Furthermore, it is
stated that the size of the cells in any given tissue after active
cell multiplication has ceased, bears a definite relation to the
original mass of chromatin contained in the fertilised egg.3
Thus it is pointed out that the mesenchyme cells of the embryo
developed from the artificially fertilised sea-urchin's egg are
only half the size of those of the embryo which has been pro-
duced by normal fertilisation, for although the parthenogenetic
and normally fertilised eggs are equal in size at the commence-
ment of segmentation, the latter possess initially twice as much
nuclear substance as the former.4
The fact that cell division ceases when the ratio of the mass
1 Minot, "The Problem of Age, Growth, and Death," Popular Science
Monthly, vol. Ixxi., 1907 ; reprinted London, 1908.
2 Boveri, Zellen-Studien, Part V., Jena, 1905.
3 Kobertson, " On the Normal Kate of Growth of an Individual and its
Biochemical Significance," Arch.f. Entwick.-Mech., vols. xxv. and xxvi., 1908.
4 Driesch, " Uber das Mesenchym von unharmonisch zusammengesetzten
Keimen der Echiniden," Arch.f. Entivick.-Mech., vol. xix., 1905.
PHASES IN THE LIFE OF THE INDIVIDUAL 661
of chromosomes in the nuclei of an egg (or of a tissue or organ)
to that of the surrounding protoplasm reaches a certain definite
limit, is regarded by Loeb l as evidence that this ratio is deter-
mined by the laws of mass action and chemical equilibrium.
He says further that if this conclusion is correct the synthesis
of nuclein compounds, from their protoplasmic constituents,
must be a reversible process.
The fertilisation of an ovum is immediately succeeded by
an enormous synthesis of nuclear material. In the cellular
division which follows, each new nucleus is of the same size as
the parent nucleus. From this fact Loeb 2 concludes that the
nucleus itself, or one of its constituents, acts as a catalyser in the
synthesis of nuclein in the fertilised ovum. Robertson,3 quoting
partly from Loeb, writes as follows : — " If the mass of the original
fertilisation-nucleus be m, the mass of nuclear material increases
during the first segmentation period to 2m, during the next to
4m, and so on in geometrical progression. The duration of the
various periods of segmentation, however, matters very little.
Hence in the first unit of time after the beginning of cell division,
a mass m of nuclear material is formed, in the second a mass 2m,
in the third a mass 4m, and so on ; thus the velocity of the
synthesis increases with lapse of time and with the mass of
nuclear material already formed. This is a characteristic of
that class of reactions known as autocatalytic, in which one of
the products of the reaction, or, in this case, one of the con-
stituents of the nucleus, accelerates the reaction. During the
process outlined above, an emphatic disproportion between
nuclear and protoplasmic material has been established. As
the nuclear synthesis becomes slower, however, the disproportion
tends to adjust itself until, finally, the growth of the organism
consists almost entirely of the growth of protoplasmic material
and in the final re-establishment of the equilibrium between
cytoplasm and nuclear material."
Robertson has investigated mathematically the quantitative
1 Loeb, The Dynamics of Living Matter, New York, 1906.
2 Loeb, " Weitere Beobachtungen liber den Einfluss der Befruchtung," &c.,
Bio. Chem. Zeitsch., vol. ii., 1906. " The Chemical Character of the Process of
Fertilisation and its Bearing on the Theory of Life Phenomena," Seventh
Internat. Congress, Boston, Univ. of California Publications, vol. iii., 1907.
3 Eobertson, loc. cit.
6612 THE PHYSIOLOGY OF REPRODUCTION
relations which exist between the amount of growth and the
time of growth. He concludes that there are two or more
growth cycles representing autocatalytic processes which make
up the total growth of an individual. In Man there are three
maxima of rate of growth, representing three phases or growth
cycles. One of these is intra-uterine, but it is probable that
this is not quite complete at birth. The second growth cycle
seems to attain its maximum annual increment at about the
fifth year, since the increment in weight at that age, as deduced
from an investigation on growth in English boys, considerably
exceeds the annual increments for the years immediately follow-
ing. A third maximum in yearly increments occurs in males
at about the sixteenth year, that is, at about the time of puberty.
In the rat, according to Donaldson.1 there are two intra-uterine
growth cycles, while there is only a single well-defined extra-
uterine cycle. Robertson suggests that the first growth cycle
in Mammals represents the course of the autocatalytic synthesis
of the nuclear substance, that the third cycle represents the
period during which cytoplasmic material is built up, while the
second growth cycle is intermediate, representing a time when
both synthetic processes go on contemporaneously.
GROWTH OF THE BODY BEFORE BIRTH
Minot 2 has recorded the results of weighing embryo rabbits
at different stages of development with a view to determining
their rate of growth. The results showed that in the period
from the ninth to the fifteenth day the young rabbit adds on an
average 704 per cent, to its weight daily, and that in the period
from the fifteenth to the twentieth day, the average daily addition
is only 212 per cent. It may be assumed, therefore, that in
younger embryos (before the ninth day) there is an increase of
over a thousand per day. Minot estimates that over 98 per cent,
of the original power of growth of the rabbit or the chick has
been lost at the time of birth or hatching, and that a similar fact
is equally true of Man. " We start out at birth certainly with
1 Donaldson, " A Comparison of the White Rat with Man in respect to the
Growth of the Entire Body," Boas Anniversary Volume, Anthropological
Papers, New York, 1906. 2 Minot, loc. cit.
PHASES IN THE LIFE OF THE INDIVIDUAL 663
less than two per cent, of the original growth power with which
we were endowed. Over 98 per cent, of the loss is accomplished
before birth — less than two per cent, after birth/' The accom-
600%
FIG. 141.— (From C. S. Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
panying diagram represents roughly the rate of growth in Man
before birth. The time intervals correspond to the ten lunar
months of gestation. The rate of increase in the first three
664 THE PHYSIOLOGY OF REPRODUCTION
months is not indicated, since there are no statistical data on
which to found any knowledge, but from the third month
onwards there are a few records available. The diagram shows
that from the third to the fourth month the increase in growth
is 600 per cent., after which it quickly drops until, during the
last month of pregnancy, it is barely twenty per cent.
GROWTH OF THE BODY AFTER BIRTH
The rate of growth from birth to maturity has been in-
vestigated most fully by Minot l in the case of the guinea-pig.
23 29 iS J9 45
FIG. 142.— (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
When this animal is born it is far advanced in development,
the period of gestation being unusually long. Immediately
after birth there is a lessening in the power of growth, a fact
which Minot ascribes to the physiological shock from which
the organism suffers as a consequence of being born. After
two or three days, however, the young are fully recovered,
and are capable of adding over five per cent, to their weight in
a single day. By the time they are seventeen days old they are
only able to add four per cent, to their weight, and by the time
they are twenty-four days old, less than two per cent. When
they have been born forty-five days, they can add only a little
1 Miuot, " Growth and Senescence," Jour, of Phys., vol. xii., 1891. " Age,
Growth, and Death," Popular Science Monthly, vol. Ixxi., 1907.
PHASES IN THE LIFE OF THE INDIVIDUAL 665
over one per cent, to their weight ; when ninety days old, less
than one per cent., and still less as they grow older, until when
about a year old they attain their full size. The curves in the
accompanying diagrams show the daily percentage increments^ _
in weight in male and female guinea-pigs respectively, as ascer-
tained by Minot. It is seen that the curve for the females is
very similar to that for the males. Both show an early period
of rapid decline in which the rate of growth is quickly diminish-
ing, followed by a period of slight decline in which the curve is
still falling, but very much more gradually. (Figs. 142 and 143.)
25811 17 Z3 23 3530 -IS
FIG. 143.— (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray. )
Minot has also investigated the rate of growth in the rabbit
and in the chicken. The young rabbit, as is well known, is born
in a very immature state of development after a relatively
short gestation period. Correlated with this fact, it was found
that the male rabbit four days after birth is capable of adding
over seventeen per cent, to its weight in a single day. From
that time the percentage increment drops very rapidly, so that
at an age of twenty-three days the rabbit can only add a little
over six per cent. After about the fifty-fifth day the decline
in the growth rate, which has hitherto been rapid, becomes
more gradual. In the case of the chicken, Minot's results were
in a general way similar, but the rate of growth on the first day
it could be measured was a nine per cent, addition to the weight,
666 THE PHYSIOLOGY OF REPRODUCTION
while the change from the initial rapid decline to the subsequent
slow decline was more gradual than in the other two animals.
TTUtfa
03813182383338 55
1062
ISO
Fio. 144. — (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
The mean weight of the foal at birth is said to be 112 pounds.
During the first three months the average daily increase is
PHASES IN THE LIFE OF THE INDIVIDUAL 667
2*2 pounds ; from three up to six months it is 1-3 pounds ; and
from six months up to three years O7 pound. It is said that
038I3I8^3^833
270
FIG. 145.— (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
probably many horses continue to grow until they are six years
old.1
1 Smith (F.), Veterinary Physiology, 3rd Edition, London, 1907.
668 THE PHYSIOLOGY OF REPRODUCTION
The calf at birth weighs about 77 pounds, and the average
daily increase during the first two years is 1-5 pounds. With
the sheep the increase is greater, for a young lamb in ten
days can add fifty per cent, to its original weight, and can
double it at the end of the first month, and treble it at the
end of the second. In pigs, however, the increase is even more
rapid, for a young pig can add twenty per cent, to its original
weight by the end of the first week, and up to the end of the
first year can add an average daily increase of 0*44 pound.
In Man growth is most rapid during the first year of life,
FIG. 146.— (From Minot's Problem, of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
when a child is able to increase its weight by 200 per cent. For
the second year this percentage drops to twenty, and for subse-
quent years up to about the age of thirteen, it fluctuates around
ten, showing a gradual tendency to decrease (but cf. Robertson,
quoted on p. 662). After this there is a distinct increase in the
percentage increment representing the prepubertal and pubertal
growth. Then there is a further decline in the power of growth,
which gradually diminishes. The prepubertal growth of girls
usually precedes that of boys, so that between the ages of twelve
and fifteen girls are often heavier and taller than boys. Boys
grow most rapidly at sixteen, girls at thirteen or fourteen.
Boys attain their full height at from twenty-three to twenty-
PHASES IN THE LIFE OF THE INDIVIDUAL 669
five years of age ; girls at twenty or twenty-one. In both sexes
the weight of the body tends to increase until about the fiftieth
year or somewhat later, owing to an accumulation of fat, but
there are of course very many exceptions.1
That good nourishment and a healthy environment favour
growth is a fact recognised by all. So also systematic exercise
has been found to increase both the weight and the height,2 and
it has been shown further that well - developed children are
more efficient mentally and take better places at school than
ill-developed and badly-nourished ones.3
1
III P&ic&nt<iq& Jncwmwite CAtck J'&malej
L
/
.
L
\ /
\
\
/
\
22K
PF
L
3#8OI832e8333846 56 66 r>_ 90 106 130 WdtvuJ 34?
FIG. 147. — (From Minot's Problem of Age, Growth, o
G-. S. Putnam & Sons, and John Murray.)
Death,
In horses and other domestic animals the effects of feeding
on growth and general development are remarkable. Thus it
is said that a highly-fed thoroughbred at two years old is
" furnished " and looks as old as an ordinary horse at four
years old.4
1 See Minot, Popular Science Monthly, vol. Ixxi., 1907. Minot states
that his calculations are based on data supplied by Professor Donaldson.
See also Lee, Article "Reproduction," in Howell's American Text-Book of
Physiology, 2nd Edition, London, 1900.
2 Beyer, "The Influence of Exercise upon Growth," Jour, of Exper.
Medicine, vol. i., 1896.
3 Porter, "The Physical Basis of Precocity and Dulness," Trans. Acad.
of Science, St. Louis, vol. vi., 1893.
4 Smith, loc. cit.
670 THE PHYSIOLOGY OF REPRODUCTION
The various other external factors that influence growth
in animals of different kinds are discussed by Morgan in his
recent work on Experimental Zoology? to which the reader
is referred for an account of the literature of the subject.
PUBERTY
Puberty, or the period at which the organism becomes
sexually mature, is marked by the occurrence of those con-
stitutional changes whereby the two sexes become fully dif-
ferentiated. It is at this period that the secondary sexual
characters first become conspicuous, and the essential organs
of reproduction undergo a great increase in size,2 while in those
animals in which during immaturity the testicles remain within
the body cavity, it is at puberty that these organs first descend
into the scrotal sacs. The puberty acceleration in growth
which takes place in Man has been already referred to. This
change is accompanied, as is well known, by alterations in the
general proportions, associated with an increase of strength,
a deepening of the voice and a growth of hair on the face and
other parts of the body. In temperate climates puberty begins
in boys at about the fourteenth or fifteenth year ; in tropical
countries it is usually a few years earlier. It is at this period
that ripe spermatozoa first make their appearance in the seminal
fluid, which is henceforward secreted in considerable quantity.
In women puberty occurs at a slightly earlier age than in
the male sex. The constitutional changes characterising this
period take place more suddenly in the female, the girl almost
at once becoming a woman, whereas the boy is several years before
he develops into a man. Moreover, the onset of puberty in the
girl is marked more precisely by the coming of menstruation,
which may make its appearance in temperate climates in the
thirteenth year. At about the same time the pelvis widens,
and the other characteristic anatomical changes take place ;
the subcutaneous layer of fat, the development of which assists
so largely in giving the body its graceful contour, is deposited ;
1 Morgan, Experimental Zoology, New York, 1907.
2 Disselhorst, " Gewichts- und Volumszunahme der maunlichen Keim-
driisen," &c., Anat. Anz., vol. xxxii., 1908.
PHASES IN THE LIFE OF THE INDIVIDUAL 671
while the internal generative organs enlarge and ripe ova are
produced by the ovary.1
In both sexes the purely physical changes of puberty are
accompanied by psychical ones which are no less pronounced,__
Both kinds of change are dependent largely, if not entirely,
upon the functional development of the generative glands.
In animals the general nature of the change which sets in
at puberty is similar to that occurring in the human species,
and the secondary sexual characters often appear for the first
time at this phase of life. Excepting in the case of the domestic
animals, little is definitely known concerning the respective ages
at which the different species become mature. Most fillies
come in use when two years old, and all by the time they are
three. Cows may come on heat when a year old, but it is best
to postpone service until three months later. A good deal
depends on nutrition, but even starved and backward cows will
receive the bull when fifteen months old. Sows will receive the
boar when eight months old, and sometimes two months earlier.
Sheep will breed at the age of six months (that is to say, lambs
born in the spring will breed in the following autumn), but the
practice is to be deprecated in the interests both of the ewes
themselves and of their lambs. Dogs will breed when about
ten months old or even earlier (sometimes seven), but the larger
kinds do not breed so soon. Cats are similar. Rodents may
breed when still younger, but whether they do so or not depends
upon the season of the year and other conditions of environment
and nutrition.
1 Runge (E.), however (" Beitrag zur Anatomie der Ovarien Neugeborener
und Kinder von der Pubertatzeit," Arch. f. Oynuk., vol. Ixxx., 1906), states
that growing follicles are by no means uncommon in ovaries of young
children. In the first year of life he found follicles of considerable size,
and in the second year still larger ones, some having a diameter of 135 /*.
In the third year degenerate follicles were also found. During this and the
following years there was a progressive increase in the size of certain of
the follicles until the ovaries became scarcely distinguishable from those
of adults excepting for their smaller size. Eunge states further that in one
instance he found a corpus luteum in an ovary of a recently born child, but
this must be regarded as very exceptional. As a result of his observations,
Runge concludes that follicular maturation sets in during infancy and not
at puberty. Ovaries of human embryos showed growing follicles only in
very rare instances.
672 THE PHYSIOLOGY OF REPRODUCTION
THE MENOPAUSE
In the male sex (as already mentioned) there is no definite
age at which the reproductive functions cease. In the female,
on the other hand, the close of the reproductive period is far
more definite, and it is this change in the human female which
constitutes the menopause or climacteric. The essential pheno-
menon of the menopause, therefore, is the permanent arrest of
all the functions connected with reproduction. It is the in-
version of the developmental process of puberty, and marks
the termination of active sexual life. In temperate climates
it almost always takes place between the ages of forty and
fifty, and most usually at about the age of forty-five.1 In
warm countries it has a tendency to be earlier, and in colder
ones later. It is usually earlier among the labouring classes,
and also in cases in which puberty was early. The actual
duration of the period when menopause symptoms occur varies
from about three to five years.
The symptoms of the menopause may be referred to two
stages — (1) a stage of menstrual irregularity, and (2) a post-
cessation stage, during which various systemic disturbances are
wont to occur. During the latter period especially the organic
functions are irregular. Palpitation, dyspepsia, sweating, and
vasomotor changes are not infrequent, and hysteria and other
psychic disturbances sometimes occur, accompanied by neuralgia,
rheumatism, and various disorders. The changes which take
place in the lower Mammals have not been studied, but they
can hardly be so great as those which occur in women.
The anatomical and physiological basis of the menopause
is, as already indicated, the atrophy of the reproductive organs.
The following are the changes which take place in women : —
(1) Senile changes in the ovary : (a) Atrophy, induration,
and shrinkage to the size of the rudimentary ovary; (6) disappear-
ance of Graafian follicles and cessation of ovarian functions.
(2) Senile changes in the Fallopian tubes : (a) shortening
and narrowing, often accompanied by obliteration of the lumen ;
(6) destruction of the epithelial cells.
1 For further details see Kelly, Medical Gynecology, London, 1908.
PHASES IN THE LIFE OF THE INDIVIDUAL 673
(3) Senile changes in the uterus : (a) Atrophy of the entire
organ, which may be reduced to a hard, wedge-shaped body,
one quarter the size of the functional organ ; (6) in many cases
closure of the internal os, or of the external os, or complete,
obliteration of the canal ; (c) consequent secretions producing
Fro. 148. — Section through ovary of woman of fifty-six, showing degeneration
of follicles and sclerosis of connective tissues. (From Sellheim.)
pyometra or hydrometra, due to the locking up of the secretions ;
(d) in some cases the disappearance of the vaginal portion,
making the upper part of the vagina continuous with the uterine
canal ; (e) degeneration of the muscular and glandular elements ;
and (/) cessation of menstruation.
(4) Senile changes in the vagina : (a) shortening, narrowing,
and loss of elasticity ; (b) loss of pavement epithelium, and
2u
674 THE PHYSIOLOGY OF REPRODUCTION
substitution of a hard surface containing cicatricial tissue ; and
(c) contraction of the entrance to the vagina.
(5) Senile changes in the vulva : (a) great contraction and
loss of elasticity, (b) destruction of glands and follicles, and (c)
cutaneous surface becoming dry and scaly.
(6) Senile changes in the mammary glands : (a) loss of
FIG. 149. — Section through uterine mucous membrane of woman of
sixty. (From Sellheim.) gl. glands.
glandular elements and cessation of function ; and (b) shrinkage
due to atrophic loss, which, however, is sometimes compensated
for by a deposition of fat.1
Other changes, depending probably on the degeneration of
the ovaries, are the assumption of certain of the secondary male
characters. These are apparently more marked in some animals
1 Dudley, The Principles and Practice of Gynaecology, 4th Edition,
London, 1905. For a further account of the atrophic changes in the uterus
and other generative organs, see Sellheim.
PHASES IN THE LIFE OF THE INDIVIDUAL 675
than they are in the human species, and have already been
mentioned in dealing with the internal ovarian secretions (p. 314).
SENESCENCE
As age advances, in addition to the menopause changes
which relate more especially to the cessation of the female
generative functions, atrophic changes of one sort or another
take place in both sexes throughout practically the entire system.
The internal spongy structure of the bones is dissolved away,
so that they are left with only a hard external shell and conse-
quently become brittle. The teeth decay and drop out. The
FIG. 150. — Section through vaginal mucous membrane of woman of
sixty-one. (From Sellheim.)
muscles shrink in volume, the actual fibres of which they are
composed becoming smaller in size and fewer in number. The
arterial walls lose their elasticity and undergo sclerosis, a
characteristic which is so constant that it has given rise to the
well-known dictum that " a man is as old as his arteries." The
tendons and ligaments also become calcified, and there is a
consequent shrinkage of stature. The size of the liver and
other viscera undergoes diminution, but the kidney and heart
retain their size ; in fact the heart is usually slightly enlarged
in old age, but this apparent hypertrophy is not associated
with an accession of power but with an increased feebleness,
and the pulse, in order to compensate for the weakness of the
enlarged heart, beats more quickly, the normal rate of seventy-
676 THE PHYSIOLOGY OF REPRODUCTION
two beats per minute rising to seventy-nine or eighty. The
rate of respiration also rises slightly, and the vital capacity of the
lungs diminishes. Moreover, the amount of carbon dioxide and
urine which are excreted becomes less. The pigment in the
hair undergoes absorption, the hair turning grey or white. The
adipose tissue beneath the skin disappears, especially in ad-
vanced old age, but fatty degeneration of muscle or glandular
tissue is not infrequent. In the male sex the prostate gland
undergoes atrophy, or in some cases a pathological hypertrophy,
which is said to be the cause of frequent penile erections.
It has been shown also that the brain decreases in size in
old age. The shrinkage begins soon after maturity, and then
continues almost steadily to the very end of life.1 Handmann 2
has published the following statistical results, which are based
on measurements carried out at the Pathological Institute at
Leipzig :—
Weight of Brain.
Age. Male. Female.
4—6 . . . . 1215 grams. 1194 grams.
7-14 .... 1376 „ 1229 „
15-49 .... 1372 „ 1249 „
50-84 .... 1332 „ 1196 „
The decrease in brain weight is accompanied by a diminution
in the thickness of the cortex and in the number of tangential
fibres present in it. These changes are associated on the
psychical side with a gradual mental failure — loss of memory,
decrease in the power of original thought and in the assimilation
of new ideas, and general decline of mental activity. Moreover,
the reaction time is lengthened, the sense organs lose their
delicacy, and in the eye the power of accommodation is largely
lost.
The minute cellular changes in the tissues are 'no less pro-
nounced. These also are in the direction of atrophy. There
is a general shrinkage in the protoplasm of the cells, but especially
in the nuclei, so that the relative amount of cytoplasmic to
nuclear 'substance becomes increased in old age. The nucleoli
1 Minot, loc. cit.
2 Handmann, «' Uber das Hirngewicht des Menschen," Arch. f. Anat. u.
Phys., anat., Abth., 1906.
PHASES IN THE LIFE OF THE INDIVIDUAL 677
also tend to disappear. Hodge * has made a comparison of the
changes in the cells of the first cervical ganglion with the follow-
ing result :—
Nucleoli observable
Volume of Nucleus. in Nucleus.
At birth . . 100 per cent. In 53 per cent.
At 92 years . . 64'2 „ „ 5 „
Thus the nucleoli are often apparently quite absent in extreme
old age. The nuclei, besides becoming smaller, grow irregular
FIG. 151. — Group of nerve cells from the first cervical ganglion of a child
at birth. (After Hodge, from Minot's Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
in shape, and in the cytoplasm there is a deposition of pigment
granules.
Senescence in men is said to commence at about the age of
fifty,2 but it is obvious that no definite limit can be assigned
to the period, since in some of the organs changes which are in
their nature degenerative begin quite early in life.
Spermatozoa continue to be produced even in quite ad-
vanced old age, and instances have been recorded of men of
1 Hodge, "Die Nervenzelle bei der Geburt und beim Tode an Alter-
schwache," Anat. Anz., vol. ix., 1894.
2 Lee, loc. cit.
678 THE PHYSIOLOGY OF REPRODUCTION
94, 96, and even 103 in whose semen active sperms were found.1
There can be no doubt, however, that the spermatozoa are
produced in far less abundance in old age.
In women the period of senescence is usually reckoned from
the menopause.
It is difficult to form any accurate comparison between the
phases of life of men and those of animals, partly because so
FIG. 152. — Group of nerve cells from the first cervical ganglion of a man
of ninety-two. (After Hodge, from Minot's Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)
C, C, cells still intact, but shrunken and loaded with pigment ;
c, c, cells which have disintegrated.
little is known regarding the conditions of natural senescence
and death in animals. Smith 2 remarks that few horses live
long enough to show much sign of arterial degeneration ; the
work they perform is the chief cause of their rapid decay, for
their legs wear out before their bodies : but, apart from this,
degenerative changes in the teeth, and more particularly the
wearing away of the molars, prevent many horses from reaching
1 Cooper, The Sexual Disabilities of Man, &c., London, 1908.
2 Smith, loc. cit.
PHASES IN THE LIFE OF THE INDIVIDUAL 679
a real old age. Blaine l has drawn the following comparison
between the age of a horse, and that of a man : — " The first
five years of a horse may be considered as equivalent to the
first twenty years of a man ; thus, a horse of five years may be
comparatively considered as old as a man of twenty ; a horse"
of ten years as a man of forty ; a horse of fifteen as a man of
fifty ; a horse of twenty as a man of sixty ; of twenty-five as
a man of seventy ; of thirty as a man of eighty ; and of thirty-
five as a man of ninety/'
THE DURATION OP LIFE AND THE CAUSE OF DEATH
Weismann, in a famous essay on the duration of life,2 and
MetchnikofT in his book of optimistic studies,3 have dealt at some
length, but from different standpoints, with the factors which
determine longevity in the animal kingdom. That the duration
of life in the various races of animals is very variable, and that,
whereas some species are remarkably long-lived, others die
after a relatively brief existence, are facts that are known to all.
Both Weismann and Metchnikoff cite numerous instances of
longevity among animals, some of the more extreme of which
may be mentioned here.
A sea-anemone belonging to the species Actinia mesembryan-
themum is known to have lived for sixty-six years, and to have
produced young, though in smaller numbers than formerly, at
the age of fifty-eight. Another sea-anemone of the species
Sagartia troglodytes, lived to be fifty years old.4 Certain marine
Mollusca are said to live for as many as a hundred years.
Among insects there is an extraordinary variability in the
duration of life, some living in a condition of maturity for only
a few days or even hours, while others (certain Hemiptera) are
believed to survive for as many as seventeen years. Moreover,
the duration of life is sometimes very different in the two sexes,
1 Blaine, Encyclopaedia of Rural Sports, London, 1858.
2 Weismann, "The Duration of Life," English Translation, in Essays
upon Heredity, &c., 2nd Edition, Oxford, 1891.
3 Metchnikoff, The Prolongation of Lif:, English Translation, London,
1907.
4 Ashworth and Annandale, " On Some Aged Specimens of Sagartia,"
Proc. Roy. Soc., Edin., vol. xxv., 1904.
680 THE PHYSIOLOGY OF REPRODUCTION
the queen ant being known to live for several years (in one case
for fifteen years), whereas the male ant survives for only a few
weeks.
Among fish, pike and carp are usually said to attain to great
ages and even to live for centuries, but there are few accurate
data.
Among reptiles, crocodiles and tortoises are known to have
long lives, a tortoise from the Galapagos Islands being stated
to have lived for 175 years.
The length of life in birds has been discussed by Gurney,1
FIG. 153. — Land tortoise (Testudo mauritanico}, aged at least
eighty-six, belonging to M. Elie Metchnikoff.
(From Metchnikofs " The Prolongation of Life ," by permission of Mr. W. Heinemanii.)
who cites several examples of great longevity, but the more
usual duration of life is from fifteen to twenty years. Canaries
are stated to have attained to twenty years of age, a herring gull
to forty-four, an imperial eagle to fifty-six, a heron to sixty, an
eagle owl to sixty-eight, a raven to sixty-nine, a swan to seventy,
and a goose to eighty. MetchnikofE records a case of a parrot
which lived for eighty- two years.
Mammals on the average appear to have considerably shorter
lives than birds. According to Weismann, whales live for some
hundreds of years, but it is difficult to see how this can be
1 Gurney, " On the Comparative Ages to which Birds Live," Ibis, vol. v.,
1899.
PHASES IN THE LIFE OF THE INDIVIDUAL 681
more than an assumption. There can be little doubt that the
great age assigned by some of the older writers to elephants
is mythical, and probably 150 years is almost the maximum
ever attained. Horses in rare cases have reached forty years^
cattle somewhat over thirty, and sheep over twenty years. A
dog is said to have lived for thirty-four years, but twenty is
usually regarded as a great age for this animal. Cats have been
FIG. 154. — Lonk sheep, aged eighteen years, with her last lamb. This sheep,
which belonged to Mr. William Peel of Knowlemere Manor, Clitheroe,
lived to be twenty-one years. It had thirty-five lambs, nine of which
were triplets.1
known to live to be twenty-one and even twenty-three, but no
greater ages appear to have been recorded.
Many instances are on record of extraordinary longevity
among men and women, but perhaps the most trustworthy is
the famous case of Thomas Parr, described by Harvey in the
Philosophical Transactions of the Eoyal Society.2 His death is
1 I am indebted to my friend Mr. W. Ralph Peel, of Trinity College,
Cambridge, for this photograph (taken by his sister, Miss Peel), and for the
information which accompanied it.
2 Harvey, "Anatomical Account of Thomas Parr," Phil. Trans., vol. Hi.,
1700. A portrait of Parr painted by van Dyck may be seen in the Royal
Gallery at Dresden.
682 THE PHYSIOLOGY OF REPRODUCTION
said to have been due to the change in his mode of life, resulting
from his migration from Shropshire to London, " where he fed
high and drunk plentifully of the best wines." " He died
after he had outlived nine princes, in the tenth year of the tenth
of them, at the age of one hundred and fifty-two years and
nine months/'
As to what factors determine the average duration of life in
different species is a problem about which there has been much
speculation. Weismann has elaborated a theory which asserts
that living matter was originally immortal, mortality first arising
in correlation with cellular differentiation. On this view the
Protozoa are potentially immortal,1 natural death occurring
only among multicellular organisms. The protoplasm of the
latter is shown to be of two kinds — germplasm, which is capable
of propagating itself indefinitely under suitable conditions like
the protoplasm of unicellular organisms, and somatoplasm,
which composes the rest of the body and is subject to natural
death. The life of the somatic cells was at first limited to one
generation, but afterwards in the higher Metazoa was extended
to many generations, and the life of the organism was lengthened
to a corresponding degree. Such a restriction went on hand in
hand with a differentiation of the parts of the organism into
somatic and reproductive cells, in accordance with the principle
of the physiological division of labour, and this process of
differentiation was controlled by natural selection. " Death
itself/' says Weismann,2 " and the longer or shorter duration of
life both depend entirely on adaptation. Death is not an
essential attribute of living matter ; it is neither necessarily
associated with reproduction, nor a necessary consequence of
it." According to this theory, therefore, the phenomena of
senescence and death, as exhibited by all the cells of the body
with the exception of the germ cells, are secondary properties
which have been preserved in multicellular organisms by natural
selection, because they are of direct advantage in the propaga-
tion of the species. An indefinite prolongation of the life of the
organism after the age of reproduction had been passed would
1 This question, about which there has been much controversy, is referred
to in Chapter VI. (pp. 212-14).
2 Weismann, " Life and Death," Essays, vol. i., 2nd Edition, Oxford, 1891.
PHASES IN THE LIFE OF THE INDIVIDUAL 683
be of no value or utility to the race, but rather a disadvantage,
since it would tend to retard the evolution of more perfectly
adapted forms of life. Furthermore, according to Weismann,
longevity, although depending ultimately upon the physiological
properties of the cells, is capable of adaptation to the conditions
of existence, and consequently is influenced by natural selection
just in the same way as other specific characters are.
Perhaps the most cogent criticism of Weismann 's doctrine of
immortality is that of Verworn, who writes as follows :— ' The
conception of living substance as immortal will be accepted by
scarcely any one who bears in mind the characteristic peculiarity
of living substance, viz., that it continually decomposes, or, in
other words, dies. There is no living substance that, so long as
it is living at all, is not continually decomposing in some parts,
while being regenerated in others. No living molecule is spared
this decomposition : the latter, however, does not seize upon
all molecules at the same time ; while one is decomposing,
another is being constructed, and so on. One living particle
affords the conditions for the origin of another or several others,
but itself dies. The particles newly formed in turn give rise
to others, and, likewise, die. In this manner living substance
is continually dying, without life itself becoming extinct." 1
From this standpoint, therefore, there can be no question of
any kind of living substance being truly immortal. The whole
conception of a possible immortality arises from a confusion of
ideas.
Minot,2 on the other hand, has elaborated a theory of
senescence which may be regarded as an extension of that
of Weismann. Like the latter, he seems to assume that
death is not a universal accompaniment of life, and that
natural death has been acquired in the course of evolutionary
development. He proceeds to define senescence as an increase
in the differentiation of the protoplasm. During the early
periods of life the young material is produced, and the proto-
plasm is undifferentiated. During the later stages of existence
cell differentiation goes on, and the organism gradually becomes
old. When the cells acquire the faculty of passing beyond the
1 Verworn, General Physiology, Lee's Translation from the second German
Edition, London, 1899. 2 Minot, loc. cit.
684 THE PHYSIOLOGY OF REPRODUCTION
simple stage to the more complete organisation, they lose some-
thing of their vitality, of their power of growth, and of their
possibilities of perpetuation. Just as senescence depends upon
the increase and differentiation of the cytoplasm, so, conversely,
rejuvenation depends upon the increase of the nuclear material ;
and consequently the alternation of the two phases of the life
cycle (the early brief one when the young material is formed,
and the later prolonged one when the process of differentiation
is going on) is due to an alternation in the proportions of nucleus
and protoplasm. In criticism of this theory, it may be urged
that it is in reality nothing more than a descriptive account of
a general type of cellular change, and that it provides no sort
of explanation as to why this type of change occurs, nor how
it is that differentiation is apparently correlated with a reduction
of vitality leading eventually to death.
Metchnikoff has laid great stress on the idea that natural
death is a rare phenomenon, at least among the higher animals.
That death with Man is frequently, if not generally, caused by
disease or accident is a fact about which there can be no disagree-
ment, and Karl Pearson l has worked out statistically the chances
of death occurring in the different phases of human life. " We
have five ages of man/' he says, " corresponding to the periods
of infancy, childhood, youth, maturity or middle age, and
senility or old age. In each of these periods we see a perfectly
chance distribution of mortality centring at a given age and
tacking off on either side according to a perfectly clear mathe-
matical law/' It was found also that the curve of mortality,
as deduced from a study of the deaths per annum of a thousand
persons born in the same year, " starts very high in infancy,
falls to its least value at thirteen or fourteen years with only
236 deaths. It then slowly increases till it reaches a maximum
in the seventy-second year of life, and falls more rapidly than it
rose, till scarcely two isolated stragglers of the thousand reach
ninety-one/' It is clear, therefore, that death from old age is
far from being the rule in the human species, but according to
Metchnikoff it seldom occurs at all.2
1 Pearson, The Chances of Death, &c., vol. i., London, 1897.
2 Metchnikoff, loc. cit.; and The Nature of Man, Mitchell's Translation,
London, 1903.
PHASES IN THE LIFE OF THE INDIVIDUAL 685
This biologist finds it impossible to accept the view that the
high mortality observable between the ages of seventy and
seventy-five indicates a natural limit to human life at about
this period. Centenarians, he points out, are not really very
rare, and he cites many cases of extreme old age, including"
that of Thomas Parr referred to above. Real old age, we are
told, is associated with an instinct for death which is as natural
as is the instinct for sleep. Metchnikoff therefore answers in
an emphatic negative the question asked by Admetus in
Euripides' Alccstis, " Is it the same thing for an old man as
for a young man to die ? " The fact that the instinct for death
seems so rarely to exist is regarded as evidence that true senility
is a comparatively infrequent phenomenon.
According to Metchnikoff, senescence is not brought about
simply as the result of arrest of the reproductive powers of the
cells. The whitening of hair in old age is due to the destructive
action of phagocytes which remove the pigment. Moreover,
hairs become old and white without ceasing to grow. Metchnikoff
believes also that atrophy of the brain is due to the destruction
of the higher nerve cells by neuronophags, and that there are
many other devouring cells which are adrift in the tissues of
aged men and animals and cause the destruction of other cells
of the higher type. The testes, however, appear to have the
power to resist these phagocytes, and with this power is corre-
lated the fact that spermatozoa are often produced even in ad-
vanced old age. MetchnikofFs theory as to the cause of death
is that it is due to the poisoning of the tissues and to the damage
done by phagocytes to those parts of the body affected by the
toxic action. He believed further that in Man and certain of
the animals this process of poisoning is brought about by fer-
mentation set up by microbial action in the large intestine.
The toxic substances produced by the intestinal fermentation
are supposed to enter the system and poison it, the result being
that the vitality of the tissues is lowered, so that they are less
able to resist the action of devouring phagocytes. The presence
of lactic acid in the intestine is believed to arrest the process of
fermentation. Metchnikoff recommends, therefore, the regular
drinking of sour milk as a means of destroying the microbes in
the intestine in the hope of prolonging life.
686 THE PHYSIOLOGY OF REPRODUCTION
The term " Death " is employed in two separate senses ; it
may mean the death of the whole body, i.e. somatic death
(this being the sense in which it is ordinarily used), or it may
be applied to the death of the individual tissues, some of which
remain alive for many hours after the body as a whole is said to
be dead. The death of the body as a whole usually occurs
suddenly. As Michael Foster says :• — " Were the animal frame
not the complicated machine we have seen it to be, death might
come as a simple and gradual dissolution, the * sans everything '
being the last stage of the successive loss of fundamental powers.
As it is, however, death is always more or less violent ; the
machine comes to an end by reason of the disorder caused by
the breaking down of one of its parts. Life ceases not because
the molecular powers of the whole body slacken and are lost,
but because a weakness in one or other part of the machinery
throws its whole working out of gear/' l
The synchronous disturbance of two or more of the bodily
functions, such as is wont to occur in old age, may destroy that
co-ordination of the various vital activities, without which life
cannot continue. The stoppage of the heart's beat is the
ordinary criterion of death, and this is a true conception, because
the cessation of the heart's movements implies the arrest of the
circulation of the blood and the consequent starvation of the
tissues of the body.
The tissues do not die simultaneously, for as already described,
some cells of the body are in process of disintegration through
the whole of life. After somatic death, the cells which make
up the nervous system usually die very rapidly. The same is
true of the gland cells ; but the muscles may remain sensitive
to external influences for many hours. In animals it has been
shown that the heart itself after removal from the body, if
kept under suitable .conditions and perfused with an artificial
fluid resembling blood serum, may continue to live and undergo
rhythmical contractions for a considerable time. In the process
of death-stiffening, or rigor mortis, the muscles once more con-
tract spontaneously, and not till this has happened is their life
utterly extinguished. Rigor mortis is brought about by the
coagulation of the muscle plasma within the cells. It begins
1 Foster, Textbook cf Physiology, Part IV., 5th Edition, London, 1891.
PHASES IN THE LIFE OF THE INDIVIDUAL 687
at periods varying from half-an-hour to thirty hours after somatic
death, and it continues for an average of about thirty hours.
Certain cells may even live for some time after rigor mortis has
passed. This is notably the case with the ciliated epithelial
cells of the inner surface of the respiratory passages, and with
the white corpuscles of the blood. Sooner or later, however,
every part of the organism perishes, putrefactive changes set
in, and the entire substance of the body passes once more to
that " dust " out of which its vital activities enabled it to build
itself up in the progress of individual life.
INDEX
[Names of authors are printed in Clarendon type, specific names in Italics.]
Abderhalden, 563 sq.
Abel and Mcllroy, 526
Abelous, 282
Abortion, 612 sqq.
Abraxas grossulariata, 639
Acmoea, 221
Acomys caharinus, 390
Actinia mesembryanthemum, 8 sq.,
679
Acton, 283
Adolphi, 177
Agassiz, 17
Ageniaspis fuscicollis, 636
Ahlfeld, 369, 497
Akutsu, 233, 259
Albatross, 27
Albers-Sehonberg, 607
Albertoni, 22
Albu and Neuberg, 266, 278
Alcyonium digitatum, 9
Allbrecht, 182, 611
Allen, B. M., 124, 153, 168
— L. M., 545
Allison, 214, 647
Alquier and Thauveny, 350
Amia, 17
Amphibia, breeding season of,
19 sqq. ; insemination in, 184 ;
fertilisation in, 190 ; fertility of,
594 sq. ; sex-determination in,
625, 637, 651
Amphioxus lanceolatus, 16
Anasa tristis, 634
Ancel and Bouin, 154, 343, 579
Anderson. See Langley and Anderson
Anguis, 151
Annandale, 7, 22, 44
Annandale and Robinson, 70
Annelida, breeding season of, 10 sq. ;
133, 205, 221
Ancestrum denned, 36
Anopheles, 13
Ant, sex-determination in, 629 ; age
of, 680
Antelope, 48, 241, 247
Antilocapra americana, 28, 305
Ape, oestrous cycle in, 63 sqq.;
fostal nutrition in, 392, 463
sqq.
Apfelstedt and Asehoff, 478
Aphidse, 11 sq., 216, 631
Arbacia, 179, 218
Arbacia pustulosa, 293, 300
Aristotle, 590
Arthropoda, breeding season of , 1 1 ;
spermatozoa of, 174 ; 307
Arvicola, 250
Arvicola agrestis, 40
Arvicola glareolus, 40
Ascaris, 128
Ascidians, fertilisation of, 207
Ascoli, 436, 481
Ash worth, 8 sq.
Ash worth and Annandale, 679
Ass, 403
Assheton, 110, foetal nutrition,
372 sqq., 376, 386 sq., 390, 394 sq.,
397 sqq., 406 sq., 419 sq., 423,
487
Astacus fluviatilis, 11
Asterias, 134 n., 204, 220 sq., 223
sqq.
Asterias forbesii, 218
Asterina, 223
Atretic follicle, 154 sqq.
Aves, breeding season of, 23 sqq.
See also Birds
Axe, Wortley, 51, 536, 618
Axis, oestrous cycle in, 49
Axolotl, 22, 189 sq., 594
B
Backhouse, 159
Badger, gestation of, 59 n. ; 416
Baer, von, 143, 145 sq., 375
Balbiani, 631
Balenoptera musculus, 52
Balfour, 116 sq., 124, 160, 379
Baliowitz, 172, 175, 178, 179^.
Bang, B., 616 sq.
- I., 293
Bar and Daunay, 498, 500, 502 sq.
Barasingha, 47 sq.
2x
690
INDEX
Barberio, 287
Bardeleben, von, 286
Barrett-Hamilton, 29
Barrows, 208
Barry, D. T., 165
M., 165, 187
Basch, 561, 577, 578
Basso, 481
Bat, breeding season of, 32 ; oestrous
cycle in, 61 sq. : maturation in,
132; ovulation in, 135, 185 ; 367,
374, 392, 407, 494; parturition
in, 541 ; fertility of, 587, 589
Bataillon, 203, 221
Bateson, 194, 198, 637, 639 sqq.,
657
Baumm, 497
Bear, breeding season of, 58 ; fer-
tility of, 590, 592
Beard, 110, 162 sq., 337, 542 sq., 628,
633, 635 sq.
Bechterew, 262, 539
Beck, 180
Beddard, 42
Bee, 186 ; sex-determination in,
626 sqq.
Beebe, 30
Beesly, 514
Beesly and Milne, 514
Bell, Blair, 69, 87, 142, 330, 346
Bende, 169
Bendix and Elstein, 297
Beneden, van, Cheiroptera, 62, 118;
maturation, 128, 131, 136, 165,
187 ; 371, 405, 459 sq., 467
Beneke, 62, 136
Benkiser, 316
Bergell and Liepmann, 481
Bergomie and Trabondeau, 607
Bernard, 431
Bernhard, 520
Bert, 571
Bertkau, 560
Bestion de Camboulas, 328
Beyer, 669
Biancardi, 517
Birds, female generative organs in,
264 sqq. ; 315 sq. ; foetal nutrition
in, 485 : breeding of, in captivity,
592 sqq. ; hermaphroditism in,
654 ; age of, 680
Birnbaum, 517
Birnbaum and Osten, 69
Birth-rate, 620 sqq.
Bischoff, 47, 55 ; corpus luteum,
143, 147, 149 sq. ; 177 ; placenta,
371, 387, 400, 421, 442
Bison, 47 sqq.
Bizzorzero and Ottolanghi, 561
Bjorkenheim, 465
Blaekman, 213
Blaine, 679
Blandford, 65
files, 5, 20, 22, 594 sq.
Bloch, 600, 614, 655
Blood, changes in, during pregnancy,
520 sq.
Blot, 510
Blumreich, 521
Bocarius, 287
Bodio, 624
Bohr, 272 sq., 434, 436, 486, 491 sq.,
508, 512, 518 sq.
Bohr and Hasseibalch, 271 sq.
Bolafflo, 585
Bombyx mori. See Silkworm moth
Bond, 347 sq.
Bondzinski and Zoja, 275
Boni, 505 sq.
Bonnet, 100, 108 sqq., 184 ; placenta,
363, 366, 371, 373, 386, 403 sqq.,
411, 413 sqq., 426 sq., 476 sq.,
480 ; 515 sq. See also Merkel and
Bonnet
Born, 624 sq.
Gustav, 337
Boruttau, 314
Bos, 208
Bossi, 185
Boston, 348
Bottazzi, 481
Bourn and Ancel, 154, 310, 343
Bouin, Ancel, and Villemin, 607
Bourne, 10
Boveri, 129, 187 sqq., 199, 660
Brachet, 253, 262, 330, 490, 538
Brady pus, 375
Braem, 658
Branca, 593
Brandt, 316
Breeding season, 4-35
Breschet, 65
Breuer and Seiler, 356
Bridge, 16
Briggs, 626
Brill, 205
Brinkmann, 380
Brocard, 510 sq.
Brock, 547
Brock, van der, 418
Brooks, 192
Brouha, 554, 560 sq., 573
Brown, 169
Brown and Osgood, 607
Brown-S6quard, 308 sq., 326, 541
Brumpt, 536
« Brunst," 36
Bryce, 138, 392
Bryce and Teacher, 369, 449, 466
sqq., 471, 474, 479
INDEX
691
Buccinum undatuw, 14
Budge, 254 sq., 259 sq., 528
Budgett, 17, 28
Buffalo, 349
Button, 591
Bufo, 203
Buhler, 145, 151
Buller, 178 sqq., 215
Bulloch and Sequeira, 351
Bullot, 221
Bunge, 265, 270, 480, 515, 563
Burchell's zebra, 202
Burckhard, 437
Burlando, 508
Burrian, 288, 296, 297
Bustard, 30
Buys and Vandervelte, 317
Calf, growth of, 668
Calkins, 6, 7, 213
Callionymus lyra, 29
Calotes jubatus, 277
Camel, rut in, 26, 49
Cameron, 48, 365
Campbell, Malcolm, 340, 595
Camus and Gley, 233, 237, 287
Canary, breeding of, in captivity,
592 ; 640, 680
Canis azarce, 55
Capaldi, 511 sq.
Caper caillie, 315
Capon, 306, 312, 349, 654
Capybara, 250
Carmiehael, 320
Carmiehael and Marshall, 317, 328,
341, 348
Carnegie, 58
Carnivora, oestrous cycle in, 53
sqq. ; uterine cycle in, 99 sqq. ;
foetal nutrition in, 386 sq., 411
sqq., 485 ; puerperium in, 551 ;
lactation in, 554 ; fertility of,
592 ; 594
Carnot and Deflandre, 68
Carp, 292
Carpenter, 208
Castle, 207 sq., 637, 639, 642, 651 sq.
Castration, chap. ix. passim, in Man,
303 ; stag, 305 ; sheep, &c., 306 ;
arthropods, 307; fowl, 311 sq. ;
frog, 313 ; effect of, on general
metabolism, 353 sqq., 656
Cat, oestrous cycle in, 56 sq. ;
superfcetation in, 159 ; acces-
sory reproductive organs in, 229,
232, 247, 252, 255 sq., 260, 262 ;
foetal nutrition in, 411, 413, 416,
418 ; pregnancy in, 512, 523 ;
525 ; female generative organs
in, 525, 528 sq., 537 ; fertility of,
591 ; growth in, 671 ; age at-
tained by, 681
Caterpillar, 307, 625
Catlin, 48 Sg.
Caton, 305
Cattle, cestrous cycle in, 46 sq.,
334 ; effects oi castration on,
306, 349 ; abortion in, 613 ;
hermaphroditism in, 652 ; hered-
ity in, 653 ; age in, 681
Cavia, 150
Cavia porcellus, 41
Caviar, 278
Centetes, 553
Centetes ecaudatus, 458
Cephalochordata, breeding season
of, 16
Ceratocephale os i.irai, 1 1
Ceratodus, 17
Cercocebus, 63, 96 sq.
Cercocebus cynomolgus, 89, 96
Cercopithecus, 63, 74 n., 584
Cercopithecus cynosurus, 65
Cervus dices, 233
Cervus elaphus, 27
Cesa-Bianchi, 161
Cetacea, oestrous cycle in, 52 sq. ;
141, 246, 375 ; lactation in, 553
sqq.
Chad wick, 15
Chcetopterus, 217, 221
Chaffinch, 315
Champneys, 85
Charrin, 515
Charrin and Goupil, 481 sq.
Charrin and Guillemont, 508
Cheiroptera, oestrous cycle in, 61
sq. ; foetal nutrition in, 459-463 ;
lactation in, 553 ; fertility in, 587
Chelchowski, 185
Chermes, 12
Chicken, growth in, 665
Child, 10
Chimpanzee, oestrous cycle in, 63
Chipman, 369, 422, 425 sq., 428,
430 sq., 487
Christ, 85
Chrysochloris, 61 n.
Cimorini, 349
Ciona intestina'is, 207
Clark, 118, 139, 145 sq., 208, 336
Clarke, Eagle, 24, 26
Cock-of-the-rock, 27
Cocks, 56, 57, 59
Cod, 278
Coelenterata, breeding season of, 7 ;
125 n. ; spermatozoa of, 174, 190 ;
200
692
INDEX
Cohen, 285
Conn, 149
Cohnstein, 520
Cohnstein and Zuntz, 434, 436,
518
Cole, 246
Collocalia, 30
Colpoda steini, 7, 214
Cook, 14
Cooper, 678
Copeman, 637
Copulatory organ, 242 sqq.
Comer, 312, 606 sq.
Corpus luteum, formation of, 142
sqq. ; false, 154 ; 334 sq. ; func-
tion of, 336 sq., 491, 502 n.
Correns, 193, 634
Coste, 358
Courant, 242
Cow, ovulation in, 136 ; 183 ; foetal
nutrition in, 386, 396 sq., 400, 403
sq., 407 ; pregnancy in, 487, 495,
508 ; parturition in, 535 ; lacta-
tion in, 553 sq., 557, 568, 571,
583 ; composition of milk of, 562
sqq. ; fertility of, 596, 608 sq. ;
artificial insemination of, 611 ;
abortion in, 616 sq. ; growth of,
668, 671. See also Cattle
Cowper's glands, 239 sqq.
Crab, 307 sq., 653
Cramer, A., 478
- H., 332, 491, 517
- W., chap, viii., 355, 431,
436, 519. See also Lochhead
and Cramer and Marshall and
Cramer
— W., and Marshall, 601
Crampton, 307, 656
Creighton, 366
Cremer, 300
Crepidula fornicata, 653
Cristalli, 511
Crocodile, 31
Crocodilus biporcatus, 277
Croom, Halliday, 65
Cross-breeding, 202-11 passim ;
effects of, 601 sqq.
Crowe, Cushing, and Homans, 356
Crowther, 564 sqq.
Crustacea, ovulation in, 137 n. ;
281 sq. ; parasitic castration in,
640; 653
Cryptorhynchus grams, 13
Ctenophora, 9
Cuckoo, 24
Cuenot, 625 sq.t 650
Culicidse, 13
Cull, 213
Cunningham, D. J., 55
Cunningham J. T., 28, 29, 151.
304 sq.
Curtis, 651
Cushing, 356
Cushny, 527 sqq.
Cuttlefish, 280
Cyclopterus lumpiis, 29
Cynthia partita, 207
D
Daels, 343, 601
Dale, 530
Dandie Dinmont, 183, 209 sq.
Daphnia, 631
Darbishire, 195
Dareste, 286
Darwin, 5, 28, 29, 201, 206, 208,
304, 307, 314 sq., 591 sqq.. 602
sq., 653 sq.
Dastre, 478
Dasyurus, 150, 158 sq., 383, 385
Dasyurus viverrinus, 149, 337
Dawson, 636
Dean, Bashford, 17
Death, 682 sqq.
Death's-Head hawk moths, 13
De Bonis, 236, 239
Decidua, and foetal nutrition, 366
sqq.
Deer, 32, 47 sq., 241 ; effects of
castration on, 305, 313 ; fcetal
nutrition in, 371, 397, 403
De Graaf, 251
Delage, 223 sqq.
Dembo, 530
De Sinety, 85
De Vries, 193
Dewar and Finn, 604
Dewitz, 178 sq.
Dinophilus apatris, 635
Dioestrous cycle, defined, 37
Dicestrum, defined, 37
Diplozoon paradoxum, 10
Dipodillus campestris, 40
Dipodillus simoni, 40, 41, 545
Discoglossus, 22
Disse, 439, 441
Disselhorst, 24, 228, 232, 241, 244,
670
Dixon, 285, 309
Doering, 145 sq.
Dog, gestation of, 32 ; cestrous
cycle in, 37, 53 sqq., 99 sqq.,
329 ; ovulation in, 135, 141 ;
artificial insemination of, 182 sq.,
203, 611 ; in-breeding in, 208
sqq. ; accessory reproductive
organs in, 229, 232, 236, 238 sq.,
252 sqq., 256, 260 ; castration of,
INDEX
309, 355 ; 349 ; influence of ovary
in, 318, 328 sq., 332 sq., 341 ;
ovum of, 371 ; f ratal nutrition
in, 387, 411, 413, 416, 427 ;
pregnancy in, 490, 498, 500 sqq.,
507 sq., 511 sq., 520 ; parturition
in, 538 ; 552 ; lactation in, 563,
583 ; fertility of, 590 sq., 601 ;
sex in, 644 sq. ; 671
Dolphin, breeding period of, 53
Donaldson, 662
Doncaster, 131, 204, 210 sq., 629,
639 sq.
Donkey, ovulation in, 136 ; 183
Doran, 330 sq., 346
Drennan, 516
Drieseh, 190, 660
Driessen, 442, 478
Droop-Richmond, 564
Drosophila ampelophilat 208
Dubner, 520
Dubois, 281, 300
Dubreuil and Regaud, 159, 344
Dubuisson, 157
Duck, 315 ; fertility of. 591 sq.
Duckworth, 306
Ductless glands, 336 ; correlation
between generative organs and,
349 sq. ; during pregnancy,
522 sq.
Dudley, 331, 674
Duesberg, 131
Dugong, 376
Diihrssen, 185
Dumas, 184
Duncan, Matthews, 66, 587, 589 sq.,
608
Dungern, 179, 216
Durham, 640
Dusing, 630, 642
Duval, 62, 361, 387, 400, 413 sq.,
416, 420, 423 sq., 426, 437, 439,
462, 483, 552
Dzierzon, 628 sq.
E
Earthworm, 186, 190
Ebner, von, 561
Echidna, cestrous cycle in, 38 sq. ;
lactation in, 554
Echinodermata, breeding season of,
15 sq. : spermatozoa of, 174, 178,
sqq., 190 ; cross-fertilisation of,
203 sqq., 210 sq. ; partheno-
genesis in, 216-226 passim
Echinoidea, 178
Echinus, 179, 300
Echinus acutus, 16
Echinus esculentus, 15, 300
Echinus microtuberculatus, 16
Eckhard, 251, 254 sqq., 577
Eden, 430, 478, 543
Eel, 18, 23
Eggelung, 554
Ehrlich, 520
Ehrstrom, 291, 507
Elmer, 62
Ejaculation, mechanism of, 251 sqq.
Eland, cestrous cycle in, 49 ; 306
I lasmobranchs, 16, 190, 277
Elephant, cestrous cycle in, 52 ; 242 ,
304 ; foetal nutrition in, 419 sq. ;
lactation in, 553 ; fertility of,
592 ; age attained by, 681
Eliomys quercinus, 40
Ellenberger, 45-6, 47, 50
Ellis, Havelock, 63, 65, 70, 71,
655
Ember iza passer ina, 593
Embryotrophe, denned, 403 n.
Empidse, 13
Emrys-Roberts, 47, 163, 435
Engelmann, 80, 83. See also Kun-
drat and Engelmann
Engstrom, 521
Enriques, 192, 214
Equus prjewalskii, 51
Ercolani, 359, 367, 401, 459
Erection, mechanism of, 251 sqq.
Erlandsen, 267
Esehrieht, 358, 375
Essen-Mpller, 342
Eunice fucata, 11
Eunice viridis, 11
Eutheria, 149
Ewart, 51, 108, 136, 159, 201 sq.,
210, 396, 545, 615 sq., 620
Exner, 234
Falco albidus, 593
Farkas, 281, 302. See also Tangl
and Farkas
Farmer, 191, 201
Farre, 359
Fehling, 512, 520
Fellner, 530
Ferret, 57 ; breeding period of, 58
sq. ; cestrous cycle of, 99 sqq. ;
ovulation in, 136, 141, 154 ;
ovum in, 371 ; 416 ; fertility of,
591, 594
Ferroni, 481, 511
Fertilisation, chap, vi., 371 ; and
sex-determination, 628 sqq.
Fertility, chap, xiv., 586
Fichera, 349
Fick, 200, 260
Finch, breeding of, in captivity, 592
694
INDEX
Findley, 84 aq.
Finn, 604
Fischel, 507
Fischer, 275
Fischer and Ostwald, 301
Fish, 184 ; biochemistry of eggs of,
277 sqq. ; age attained by, 680
Flatau, 342
Fleming, 536, 608
Flemming, 156 sqg.
Fletcher, 253
Flies, sex- determination in maggots
of, 626
Florence, 287
Flower, 43
Flower and Lydekker, 554
Foa, 320, 572, 580 sq., 583
Foetal membranes, 377 sqq.
Foges, 311, 579
Fogge, 258
Foote and Strobell, 634
Fordyce, Dingwall, 74, 568
Forel, 655
Foster, 540, 686
Fothergill, 369
Foulis, 118
Fowl, oviduct of, 24, 333 ; ovula-
tion in, 139 n. ; 184 ; Andalusian,
194 sq. ; biochemistry of the
sexual organs of, 264 sqq. ; 311
sq., 315, 320 n., 349; foetal
nutrition in, 435, 485, 487 ;
fertility of, 589, 590, 605 ; hered-
ity in, 640 ; hermaphroditism in,
651 n., 654
Fowler, 305
Fox, breeding season of, 55
Fraenkel, 118, 161, 334, 338 sqq.,
353
Fraenkel and Conn, 338
Franck-Albrecht-Goring, 545
Francois-Franek, 251, 255
Frankenhauser, 528
Franz, 527, 612
Frazer, 70, 602
Free-Martin, 652
Freund, 350, 493, 522, 524
Friedlander, 548
Fries, 59 n.
Frog, breeding season of, 20 sqq. ;
maturation in, 133 ; oviposition
in, 140, 141 ; insemination in,
184 ; fertilisation in, 187, 216,
221 ; 234, 277, 278, 300 ; experi-
ments on testes of, 312 sqq., 350.
See also under Rana
Frommel, 366, 494
Furbringer, 236, 287
Furth, von, 280
Furth, von, and Schneider, 481
Gadow, 20, 23, 24
Gadus morrhua, 291
Galabin, 66, 83, 86, 139, 160, 533 sq.,
615
Galago agisyrnhanus, 396, 410
Galeopithecus, 377
Galeopithecus volans, 98
Galgulus oculatus, 634
Gallus bankiva, 591
Gamecock, 653
Gametic selection, 202 sqq.
Gamgee, 267, 401
Garner, 63
Garrod, 247
Gaskell, 254, 350
Gassner, 497, 547 sq.
Gasteropods, 133
Gautier, 181 sq.
Gawronsky, 526 •
Gayal, oestrous cycle in, 49
Gazella dorcas, 49
Gazelle, 247
Gebhard, 84 sq., 87 sq., 89
Geddes and Thomson, 30, 164, 165,
175, 191, 623, 626 sq., 646 sq.,
651
Gellhorn, 74, 576, 584
Geppert, 514
Gerbillus hertipes, 40
Gerhardt, 141, 244
Gerlaeh, 132
Gestation in Mammalia, 32 ; guinea-
pig, 42 ; sheep, 46 ; cattle, 47 ;
camel, 49 ; sow, 50 ; mare, 51 ;
elephant, 52 ; dog, 54 ; wolf, 55 ;
fox, ib. ; Cape hunting dog, ib. ;
domestic cat, 56 ; wild cat, 57 ;
lioness, 58 ; tigress, ib. ; puma,
ib. ; bear, ib. ; badger, 59 n. ;
walrus, 60 ; hedgehog, 61 ; apes
and monkeys, 65 ; duration of,
73 sq., 544 sq.
Geyelin, 590
Geyl, 543
Giacomini, 151, 380
Giacosa, 277
Gierke, 508
Gies, 222, 300
Gilbert, 247
Gilchrist and Jones, 564
Giles, 68, 547
Giraffe, oestrous cycle in, 49, 247 „
400
Girtanner, 358
Glass, 331
Gley, 240. See also Camus and
Gley
Gnu, oestrous cycle of, 49
INDEX
695
Goat, cestrous cycle in, 64 ; in-
breeding in, 214; 231; lactation
in, 555, 558, 567, 571 sq., 584
Godet, 431
Godlewsky, 199
Godman, 67
Gofton, 142
Gohre, 463
Goltz, 22, 253, 329, 490, 538
Goltz and Ewald, 329, 490, 538,
577
Goodsir, 358 sq.
Goose, fertility of, 591 sq.
Gordon, 331, 607
Gorilla, oestrous cycle in, 63
Gottschalk, 477
Gottschau, 350
Graefe, von, 342
Grass!, 627
Grass! and Sandias, 627
Griffiths, 238, 240
Grigorieff, 319
Grohmann, 48
Gross, 306
Grouse, 315
Gruber, 235
Gruenhagen, 253
Grunbaum, 579. See also Gurber
and Grunbaum
Guaita, von, 208
Gudger, 652
Guillot, 513
Guinea-fowl, 635
Guinea-pig, maturation in, 132 ;
ovulation in, 135 ; 150, 156 ; arti-
ficial insemination of, 183, 234 ;
male accessory reproductive
organs in, 232, 234, 236; 273,
286 ; castration in, 306, 310,
349 ; ovariotomy in, 320, 343 ;
328, 349 ; foetal nutrition in,
374, 400, 439, 442-7, 466 ; lacta-
tion in, 568, 578 ; fertility of,
590, 607 ; growth in, 664 sq.
Guldberg and Nansen, 53
Gull, breeding of, in captivity, 592
Gunther, 184, 251
Gurber and Grunbaum, 508
Gurney, 315, 680
Gusterosteus spinachia, 30
Guthrie, 320
Guyer, 635, 657
Gymnura, 61, 377
Haddon, 600, 614
Hagemann, 54, 500 sqq., 504
Halban, 320, 332, 334, 492, 524,
579, 581 sq.
Haldane, 52
Haller, 400 sq.
Halliburton, 562, 564
Hamm, 165
Hammarsten, 264, 277, 278
Hammond, 606
Hamster, 241
Handmann, 676
Hare, 588
Harper, 139 sqq.
Harrington, 17
Hart, Berry, 652
Hart and Gulland, 366
Hartung, 266
Harvey, 187, 357, 400, 681
Hasselbalch, 274. See also Bohr
and Hasselbalch
Hausmann, 135
Haycraft, 71
Heape, 26, 32 sq. ; the cestrous
cycle, chap, ii., passim, 79, 85
sqq., 89-97 passim ; the ovary,
127, 133-9, 154, 158, 163 ; in-
semination, 180-5 passim, 609
sqq. ; 209, 330, 334 sq. ; placenta,
372 sq. ; 495, 583 sq., 596 sq.,
617 sqq. ; sex-determination,
641-6
" Heat," 26, chap, ii., passim ; and
menstruation, 110, 329 sqq. ; and
ovulation, 135 ; cause of, 320
Hedgehog, breeding season of, 60
sq., 238; 240, 252, 337; foetal
nutrition in, 367 sqq., 374, 377,
390 sqq., 420, 447-452, 469 ; 552
Hegar, 304
Heidenhain, 560 sq.
Heil, 74
Heim, 282
Heinrieius, 364, 414, 416, 521
Helme, 527 sq., 530, 549
Hemitragus jerulaicus, 47, 48
Henderson, 349, 550
Henking, 633
Henneguy, 156
Hennig, 366
Henriques and Hansen, 270
Hensen, 371, 443
Herbst, 220, 315
Herdman, 17
Herff, von, 329, 526
Hergesell, 138
Herlitzka, 320
Hermaphroditism, 650 sqq.
Heron, 621
Herring, 279, 297
Hertwig, 187, 191, 217, 219, 376,
389
Herwerden, van, 60, 62, 63, 89, 96
sqq., 137, 536
696
INDEX
Heukelom, von, 460, 470, 473
Hewitt, 13, 131, 226
Hickson, 199 sq.
Hikmet and Regnault, 304
Hildebrandt, 491, 581
Hilger, 277
Hill, 149, 384 sq., 576, 585
His, 143, 146, 162, 364, 463, 466
Hobday, 332
Hodge, 677
Hofacker, 646
Hofbauer, 362 sqq., 479 sqq., 486,
489, 512, 516, 550
Hoffmann, 369 sq.
Hofmeir, 316
Hofmeister, 274, 510, 572
Hogue, 226
Holdich, 305
Hollard, 421
Holophytum, 9
Holzbach, 346
Homans, 356
Home, 189, 609
Honor§, 126 sq., 144
Hopkins and Pinkus, 274
Horse, 229, 234, 252 ; effect of
castration on, 307, 310 ; fertility
of, 599 n., 604 sq. ; 612 ; sex-
determination in, 643 ; growth
in, 666 sq., 669, 671 ; age at-
tained by, 681. See also Mare
Hewlett, 13
Hubrecht, placenta, 361, 367 sqq.,
376 sqq., 391-486 passim, 494
Hugounenq, 514
Huish, 183, 610 sq.
Hunter, A., 289
— v- John, 184, 315, 358 sq., 466,
609
- William, 358
Hurst, 194
Hutchinson, Woods, 350
Huth, 214
Huxley, 375 sqq.
Hybrids, fertility of, 603 sq. ; 612
Hydatina, 630
Hydatina senta, 632, 635, 638
Hydra orientalis, 7
Hydromedusae, 190
Hyena, 250
Hylomys, 61
Hyrax, 387, 420
Ibex, 47 sq.
Ihering, yon, 636
In-breeding, 208 sq. ; effects of,
601 sqq.
Infusoria, 6, 200
Ingerslev, 520
Insecta, spermatozoa of, 178, 190
Insectivora, oestrous cycle in, 60
sq. ; fostal nutrition in, 390 sqq.,
447-459
Insemination, artificial, 181 sqq.,
609, sqq.
Issakowitsch, 632, 644
Iwanoff, 135 sq., 183, 234, 237, 604,
609 sq., 612
S;
Izuka, 11, 134
Jacob, 530
Jacobi, 18, 184
Jagerroos, 484, 501, 516
Jankowski, 149 sq.
Janosik, 156 sq., 217
Jassinsky, 360
Jeannin, 523
Jenkinson, 188 sqq., 220, 373, 404,
406, 439 sq., 442, 487
Jenner, 24
Jennings, 215
Jentzner and Beuthner, 328
Joukowsky, 212
Julin, 118
K
Kahlden, von, 85
Kallius, 526
Kaltenbach, 510
Kangaroo, 39
Kastschenko, 360, 362 sq., 475
Kazzander, 108, 110
Kehrer, 140, 316, 498, 507, 527
Keiffer, 100, 529 sq., 541, 581
Keilmann, 541
Kellogg, 307, 626
Kelly, 608, 614, 621, 672
Kennedy, 66
Kerr, 18, 28
King, 625, 636
Kirkham, 132
Kirsten, 510
Klebs, E., 360
C* Q
Klein, 368, 478
Kleinhaus and Schenk, 343
Knauer, 318 sq., 332
Knott, 584
Kobelt, 251
Kolliker, 118, 143, 146, 156, 158,
165, 236, 252, 359, 561
Kollmann, 467, 494
Kolster, 108, 233, 397, 403, 413, 437,
439, 442
Korner, 528
INDEX
697
Kossel, 269, 275, 288 sq., 292, 293,
298
Kossel and Dakin, 292
Kossel and Kutseher, 291
Kossel and Pringle, 291
Kostanecki, 224
Krafft-Ebing, 655
Kraft, 180
Kraus, 513
Kronig, 353, 548
Kruieger and Offergeld, 490, 538
Krukenberg, 265, 277, 282
Kuhne and Ayres, 243
Kundrat and Engelmann, 163, 548
Kupelweiser, 205
Kurdinowski, 527 sq., 530 sq.
Kworostansky, 479
Lacertilia, 380
Lactation, and the oestrous cycle,
74 ; and pregnancy, 138 n.,
chap. xiii. ; and fertility, 600
Ladenburg and Abel, 285
Lamprey, 190, 221
Landwehr, 233, 286, 572
Lane-Claypon, 118, 122 sqq., 148,
150. 160 sq., 168, 344
Lane-Claypon and Starling, 333, 573,
578 sqq.
Lang, 186
Lange, 523
Langer, 560
Langhans, 359 sqq., 366, 477
Langley, 255, 259, 525, 529
Langley and Anderson, 252 sq.,
255 sqq., 259, 260 sq., 525, 529
Langstein and Neubauer, 507
Lannois and Roy, 306
Lanz, 511
Lark, 27
Lataste, 41, 106, 233
Lauder, 564
La Valette St. George, 173
Laycoek, 31, 65, 66, 316
Leathes, 482
Lebedeff, 520 sq.
Lecaillon, 310
Ledermann, 400
Lee, 669, 677
Leeney, 536
Leersum, 506
Leeuwenhoek, 165, 184
Lefevre, 224
Lefroy, 13
Lehmann, 558, 566
Lemaire, 510
Lemur, oestrous cycle in, 62, 97 sq. ;
ovulation in, 137 ; foetal nutri-
tion in, 377, 396, 410 ; fertility
of, in captivity, 593 n.
Lemur oidea, foetal nutrition in,
408 sqq.
Lenhossek, von, 363 sq.
Leopold, 83 sq., 366, 467, 548
Lepidoptera, 13, 639
Lepidosiren, 18, 28
Lepidosteus, 17
Lepus, 150
Lepus cuniculus. See Rabbit
Lepus varidbilis, 41
Leslie, 21
Leuckart, 233
Leusden, 549
Levene, 278, 294
Leydig, 240
Liebermann, 271, 274
Liepmann, 493
Lillie, 52, 221
Limnoea, 14
Limon, 320, 351
Linnet, 593
Linton, 241
Lion, 247
Lioness, oestrous cycle in, 58
Lipes, 80, 82, 85 sq.
Littlejohn and Pirie, 288
Littorina, 14, 15
Lo Bianco, 14, 16
Lochhead, chap, x., 435 sq.
Lochhead and Cramer, 269, 273,
302, 431, 433, 435, 496, 508
Lock, 191, 196
Lode, 176, 232, 234, 283
Loeb, A., 258
- Jacques, 191, 204 sq., 218 sqq.,
299 sq., 301 sq., 661
L., 150, 156, 344
Loewenthal, 162, 347
Loewy, 312, 356
Loewy and Richter, 355
Loisel, 170, 329
Lombroso and Bolaffio, 585
Longridge, 546 sq., 549, 551
Lota vulgaris, 291
Lott, 177
Lottia, 221, 224
Lov&i, 251
Low, 46, 208
Lubarseh, 286
Lucas-Champonniere, 343
Lucien, 151
Lusk, 563
Liithje, 354 sq.
Lycaon pictus, 55 sq.
Lydekker, 42, 43, 46. See also
Flower and Lydekker
Lyre-bird, 30
698
INDEX
M
Macacus cynomolgus, 64
Macacus fascicularis, 64
Macacus nemestrinus, 63, 65, 373
Macacus rhesus, 63 sq., 89 sqq., 96,
259
Macacus sinicus, 64
Macallum, 297
Macbride, 204
McClung, 130, 633
McFadyean, 609
Macgregor, 89
M' In tosh and Master man, 205
Mcllroy, 526
Mclvor, 644
Mackerel, 293
MacLean, 23
Maerdervort, 85
Magnus-Levy, 497, 499, 506 8q., 519
Magnus-Levy and Falk, 356
Maja, 282
Maja squinado, 281
Majert and Schmidt, 285
Malthus, 620
Maly, 281
Mammalia, breeding season of,
26 sqq. ; cestrous cycle in, chap,
ii. ; spermatozoa of, 174 ; ferti-
lisation in, 190 sq., 203 ; female
generative organs in, 263 sq., 273 ;
placental classification of, 375 sqq.
Man, oestrous cycle in, 65 sqq. ;
menstrual cycle in, 75 sqq.,
161 sqq., 334 ; ovulation in,
131^ sqq. ; spermatozoa in, 172 sqq.;
artificial insemination in, 184,
609 ; accessory reproductive
organs in, chap. vii. ; castration in,
304; ovariotomy in, 314, 316 sq.,
330 sqq. ; foetal nutrition in, 371,
380, 384, 388, 392, 402, 463-483
passim, 487 ; changes in the
maternal organism during preg-
nancy in, chap. xi. passim ;
innervation of female generative
organs in, 525 sqq. ; parturition
in, 531 sqq. ; prolonged gestation
in, 544 sq. ; puerperium in,
545 sqq. ; lactation in, 553, 562,
566 sqq. ; fertility in, chap. xiv.
passim ; sex-determination in,
636 sqq. ; 653, 655 ; growth in, 662
sqq., 668 sq. ; puberty in, 670 sq. ;
menopause in, 672 sqq. ; sene -
cence in, 675 sqq. ; age attained
by, 681 sq.
Mandl, 85, 88, 526
Mandl and Burger, 346
Manis, 375
Manouvrier, 655
Mansfeld, 268
Marchal, 636
Mare, cestrous cycle of, 50 sq. ;
ovulation in, 136 ; 159 ; artificial
insemination of , 183, 185, 610 sq. ;
telegony in, 201 sq. ; in-breeding
in, 208, 214 ; ovariotomy in, 332 ;
fcetal nutrition in, 396 sq., 403
sq. ; parturition in, 535 sq. ; ges-
tation in, 545 ; lactation in,
554, 583 ; fertility of, 595, 605 ;
abortion in, 613, 615 sqq., 619, 654
Markhor, 47 sq.
Marmot, cestrous cycle in, 105 sq. ;
corpus luteum in, 149, 247
Marshall, F. H. A., the oestrous
cycle, 35, 42, 99, 136 ; the
corpus luteum, 147, 148, 152 ;
154, 202, 247, 268 ; fcetal
nutrition, 431, 436 ; fertility,
595 sq., 598, 604, 613, 618.
See also Carmichael and Mar-
shall ; Cramer and Marshall ; and
Simpson and Marshall.
Marshall, F. H, A., and Cramer, 495
Marshall, F. H. A., and Jolly, 35,
53, 56, 58, 99, 135, 184, 320,
321, 332, 341, 348, 491, 504,
579
Marshall, F. H. A., and Kirkness,
572
Milnes, 78
Marsupialia, cestrous cycle in, 39 ;
141, 149, 246 ; corpus luteum in,
339 ; fcetal nutrition in, 381 sqq. ;
lactation in, 554 ; mammary
glands in, 576
Martin, 69, 86
Masius, 427, 430
Masquelin and Swaen, 366, 423-4,
494
Mast, 208
Masterman, 16,205. See also M'Intosh
and Masterman
Matthes, 480
Matthews, 134, 224, 293, 297, 505
Maturation, 125 sqq. ; rabbit, 131 ;
mouse, 132 ; guinea-pig, ib. ; bat,
ib. ; mole, 133 ; pigeon, ib. ;
frog, ib. ; Invertebrates, 133-4
Maupas, 212 sq., 630, 632
Maurel, 498, 508
Maximo W, 425 sqq., 430 sq.
Mayo-Smith, 71
Mayow, 358
Mead, 217
Meade-Woldo, 59
Meckel, 232
Meisenheimer, 307
INDEX
699
Mendel, 193 sqq.
Mendel and Leaven worth, 269
Menopause, 353, 672 sqq.
Menstruation, in Primates, 62 sqq. ;
in Man, 65 sqq., 75 sqq., 161 sqq. ;
and lactation, 74, 334, 569 ; and
" heat," 329 sqq. ; 346, 350
Merconitski, 268
Meredith, 331
Merganser, 315
Meriones longifrons, 40, 545
Meriones shawi, 40, 41, 545
Merkel, 169
Merkel and Bonnet, 526, 561
Merletti, 481
Merttens, 473, 478
Metaphyta, 7
Metazoa breeding season of, 7
Metehnikofl, 78, 111, 163, 679 sq.,
684 sq.
Metoestrum, defined, 37
Michaelis, 570
Michel, 499
Miescher, 18, 279, 288 sq., 292 sq.,
295 sqq.
Milk, uterine, 400 sqq. ; composi-
tion and properties of human and
cow's, 562 sqq. ; influence of
diet, &c., on yield of, 564 sqq. ;
discharge of, 569 ; formation of
organic constituents of, 569 sqq.
Millais, 48, 52, 53, 55 sq., 59 sqq.,
183
Milroy, 19, 279
Mingazzini, 151
Minot, 79, 86, 202 ; foetal nutri-
tion, 362, 366, 388, 421, 463 ; 542,
590; growth, 660, 662, 664 sqq.,
676, 683
Miotti, 511
Mironow, 578
Misuraea, 232
Mislawsky and Bormann, 258
Mobius, 30
Mohrike, 63
Mole, breeding season of, 61 ;
maturation in, 133 ; accessory
reproductive organs in, 232, 238,
240 ; ovum in, 372 ; foetal nu-
trition in, 376 sq. ; 392, 456-7,
485
Mollusca, breeding season of, 13 sqq.,
205
Monkeys, cestrous cycle in, 62 sq. ;
menstrual cycle in, 89, 335 ;
ovulation in, 137, 330 ; 255 ; foetal
nutrition in, 392, 463 sqq. ; fer-
tility of, 592
Monoestrous, definition of, 38
Monotremata, oestrous cycle in, 38
sq., 141 ; 244; corpus luteum in,
339 ; 357 ; lactation in, 554, 584
Montgomery, 129
Moore and Parker, 571
Morat, 254
Morgan, 8, 12, 140, 199 ; fertilisa-
tion, 207, 208, 216 sq. ; 305, 604;
sex-determination, 623, 625, 635
sq., 641 sq., 648, 670
Morieke, 84 sq.
Morner, 274, 279
Morris, 331
Mosher, 68
Mouse, 40 ; ovulation in, 135 ; 156 ;
artificial insemination of, 183 ;
373 sq., 389; foetal nutrition in,
420, 437-442, 449, 494 ; 545, 605,
611 ; sex in, 647, 650
Mule, 203, 584
Muller, A., 253
- F., 519
Fritz, 207
— P., 606
Muller and Masuyama, 277
Muntz, 572
Murlin, 503, 507, 518
Mus, 150
Mus decumanus. See Rat
Mus minutus, 40
Mus musculus. See Mouse
Mus rattus, 40
Mus sylvaticus, 40
Musk deer, 241
Musk ox, 49, 249
Musk rat, 241
Mustelus Icevis, 277, 380
Myliobatis, 151
Mytilusy 205
N
Nagel, 117, 145, 177, 240, 260, 533
Nasse, 520 sq.
Nathusius, 46
Nattan-Larrier, 370, 492
Needham, 400
Nematodes, 133, 174
Nematus ventricosus, 627
Nemertea, breeding season of, 10
Neugebaur, 651
Neumann and Vas, 356
Neumeister, 277, 569
Newbigin, 29
Newcomb, 646, 650
Newport, 187
Newsholme and Stevenson, 621
Newt, 23, 184, 300
Nicholson, 522 sq.
Nicolas, 247
Nightingale, 25
700
INDEX
Nikolski, 255
Niskoubina, 344
Nitabuch, 477
Nolf, 367, 419, 460 sqq.
Noorden, von, 68, 354, 356, 497, 510,
513, 515
Nudibranchs, 14
Nussbaum, 141, 312 sq., 632
Nycticebus, 408
Nylghau, oestrous cycle in, 49
O
Oceanu and Babes, 356, 567
Ocneria dispar, 307
Oddi and Vicarelli, 519
CEstrus or CEstrum, defined, 36
(Estrous cycle, chap, ii., 335
Offergeld. Sec Kruieger and Offer-
geld
Oliver, 83, 85, 138, 614
Onchorhynchus, 30 n.
Onuf, 253
Oogenesis, chap. iv.
Ophelia, 221
Ophiothrix fragilis, 204 n.
Opossum, 385, 484
Orang-utan, restrous cycle in, 63
Ornithodelphia, 380
Ornithorhynchus paradoxus, 149
Orton, 653
Orycteropus, 375
Os borne and Campbell, 275
Oser and Schlesinger, 537
Oshima, 512
Ostwald, 300 sq.
Ott, 67, 68
Otter, breeding season of, 59 ; 416
Oudemans, 239, 307
Ovariotomy, 314, 316 sqq. ; and
menstruation, 330 sqq. ; and preg-
nancy, 341 sqq.
Ovary, changes in, during the
oastrous cycle, chap. iv. ; in-
fluence of, 314 sqq. ; Man, 314
316 sq., 330 sqq. ; deer, 314
poultry, 315 sq. ; rabbit, 317 sqq. ,
guinea-pig, 320 ; rat, 321 sqq.
internal secretions of, chap. ix.
passim ; innervation of, 526
Overlach, 366
Ovis, 150
Ovis ammon, 43
Ovis argali, 43
Ovis burrhel, 42 sq.
Ovis canadensis, 43
Ovis musimon, 42
Ovis poli, 43
Ovis tragelaphus, 42
Ovis vignei, 43
Ovulation, 125 sqq. ; rabbit, 134 ;
mouse, 135 ; rat, ib. ; guinea-pig,
ib. ; dog, ib. ; sow, ^6. ; ferret,
136, mare, ib. ; donkey, ib. ; cow,
ib. ; sheep, ib. ; bat, 136 sq. ;
Primates, 137 ; Man, 137 sqq. ;
Invertebrata, 137 n. ; and men-
struation, 330, 333 n., 335
Ovum, formation of, 160 sq. ;
chap, x., part ii., passim ; the
ovarian, 370 sq. ; the fertilised,
371 sqq.
Owen, 31, 42, 61, 247, 359
Ox, 288, 296, 306, 349, 486
Pachyuromys dupra&i, 41
Paladino, 146
Palolo worms, 10 sq., 134
Paludina, 175, 633
Papio, 63
Papio porcarius, 64
Paramoecium, 6, 212 sqq.
Paramcecium caudatum, 211
Parthenogenesis, 216 sqq.
Parturition, 527 sqq. ; human,
531 sqq., 538 ; other Mammalia,
535 sqq. ; nervous mechanism of,
537 sqq.
Patella, 14, 216, 224 n.
Paterson, 143, 365
Paton, Noel, 18, 19, 278 sq., 349,
496, 508
Paton, Kerr, and Watson, 434, 508
Payer, 511, 520 sq.
Payne, 634
Pearl, 211
Pearl and Surface, 333, 605, 651
Pearson, Karl, 202, 605, 684
Pearson, Lee, and Bramley-Moore,
605
Peel, 681
Pelican, 30
Pelikann, 235
Pelodytes, 203
Pembrey, 272
Pepere, 349
Perameles, 39, 339, 384 sq.
Perch, 277 sq.
Perez, 158, 176, 217, 629
Peripatus, 11
Perry-Coste, 72
Peters, 361, 366, 466 sq., 469, 471,
473, 479, 515
Petrel, stormy, 26
Petrunkewitsch, 628 sq.
Pfannenstiel, 264, 368
Pfeffer, 215
INDEX
701
Pfister, 578
Pfluger, 114, 116, 124, 143, 203,
313 aq., 329, 436, 518
Pfluger and Smith, 203
Phalarope, 30
Phascolarctus cinereus, 39
Pheasant, 315
Phylloxera, 635 sq.
Piccolo and Lieben, 263
Pick and Pineles, 523
Pi6ri, 299
Pig, 208, 371, 668. See also Sow
Pigeon, maturation in, 133 ; ovula-
tion in, 139 sqq. ; fertility of
591 sq.
Pinard, 545
Pine-marten, breeding season of, 59
Pisces, breeding season in, 16 sqq. ;
spermatozoa in, 174 ; fertilisa-
tion in, 190
Pittard, 306
Pizon, 222
Placenta, as an organ of nutrition,
chap, x., 491 sqq.
Placotus, 148
Plaice, 17
Plimmer, 270, 275
Plimmer and Scott, 268
Plonnis, 183, 611
PIoss, 70
Plover, golden, 25
Pocock, 63 sqq., 96, 137, 306
Poehl, 236, 285, 309
Polaillon, 532
Polecat, breeding season of, 59
Polynoe, 224
Polyoestrous, definition of, 38
Polyphemus, 174
Polypterus, 17, 28
Polypterus bichea, 17
Polypterus laprodei, 17
Polypterus senegalis, 17
Polyspermy, 190
Poncet, 306
Porcher, 571 sqq.
Porpoise, breeding period of, 53
Porter, 669
Potthast, 54
Potts, 308, 640, 653, 658
Praopus hybridus, 636
Pratt, 9
Pregel, 309
Pregnancy, 138 n., chap. x.
passim ; changes in the maternal
organism during, chap. xi. ;
body-weight during, 497 sq. ;
protein metabolism in, 498 sqq. ;
carbohydrate metabolism in,
507 sqq. ; metabolism of fats in,
511 sqq. ; metabolism of metals
and salts in, 514 sqq. ; respiratory
exchange during, 517 sqq. ;
changes in maternal tissue during,
520 sqq.
Prenant, 336
Prepotency, denned, 206 n.
Pr6vost, 184
Preyer, 358, 365
Primates, oestrous cycle in, 62 sqq. ;
ovulation in, 137 ; 374 ; foetal
nutrition in, 392 sqq., 402, 463-
482, 484 ; lactation in, 553
Prjewalsky, 43
Proboscidia, foetal nutrition in, 387
sq., 419 sq.
Prochownick, 496
Prooestrum, defined, 36 ; signifi-
cance of changes diiring, 161 sqq,
Prostate gland, 235 sqq.
Protopterus, 18
Protozoa, breeding season of, 6 sq. ;
200 ; conjugation in, 211 sqq. ;
immortality of, 682
Przibram, 134, 190
Pteropus, 62
Pteropus edulis, 462
Puberty, 670 sq.
Puerperium, 545 sqq.
Puma, oestrous cycle of, 58
Punnett, 194, 624, 632 aq., 639 aq.,
649, 657
Punnett and Bateson, 639
Purpura lapillus, 14
Pussep, 254
Pyrrhocoris, 633
Quagga, Lord Morton's, 201
R
Rabbit, oestrous cycle in, 37, 41,
105 sqq. ; changes in the ovary of,
123, 128, 131, 134 aq., 139, 144,
149, 154, 156, 158 sq., 160 ;
spermatozoa of, 177, 180 ; artifi-
cial insemination of, 183 sq., 234;
fertilisation in, 187; in-breeding-
in, 214 ; accessory reproductive
organs in, 232, 252, 254 sqq., 260 ;
269, 273 ; ovariotomy in, 317 sqq.,
338 ; 328, 343 sq. ; hysterectomy
in, 347 sq. ; 349 ; foetal nutrition
in, 369, 372 sqq., 380, 388 sqq.,
405, 420-436, 481, 483, 486 aq.,
489 n. ; pregnancy in, 494 sqq.,
498, 500 aq., 508, 512, 515;
female generative organs in, 525,
527 sqq. ; parturition in, 537 ;
lactation in, 553 ; growth of
702
INDEX
mammary glands in, 573 sqq.,
578 sgq. ; fertility of, 588, 591,
594, 601, 607 : sex in, 643 ;
growth in, 662, 665
Raciborsky, 47, 138
Raja, 277
Raja batis, 636
Rana arvalis, 203
Rana fusca, 202 sq.
Rana limnocharis, 22
Rat, osstrous cycle in, 37, 40,
105 sqq. ; changes in the ovary
in, 123 ; ovulation in, 126 ; 135,
183, 234, 236 ; influence of ovary
in, 321 sqq., 341, 343 ; hysterec-
tomy in, 348 ; 355, 368 ; ovum in
372; 389, 420; parturition in,
536 ; lactation in, 555, 579 ;
fertility in, 587, 595 ; 637 ; sex
in, 650 ; growth in, 662
Rauber, 365
Raudnitz, 564
Rauther, 233 sq.
Raven, 26
Ray, 358
Reaumur, 12
Redstart, 315
Regaud and Dubreuil, 607
Regaud and Policard, 336
Regnard, 514
Rehfisch, 231
Reichert, 442 sq.
Reid, 358 sq.
Rein, 537
Reinke, 286
Reinl, 67, 68
R6my, 259
Rengger, 55
Repreff, 499
Reptilia, breeding season of, 23 ;
fertilisation in, 190 ; 273
Retraction, mechanism of, 251 sqq.
Retterer, 100, 251, 254
Retzius, 175
Rhacophorus leucomystax, 22
Rhinoceros, 247
Rhodites, 638
Ribbert, 314, 319, 578, 656
Rieder, 520
Rielander, 481
Riemann, 528, 537
Ries, 335
Rink, 54
Robertson, 660 sqq.
Robinson, 371 sqq., 376, 389, 395
411, 413, 416
Rodentia, oestrous cycle in, 40 sqq.
232 n., 241 ; accessory reproduc-
tive organs in, 244, 246 sq. ; foetal
nutrition in, 388 sqq., 420 sqq, ;
gestation in, 545 ; puerperium
in, 551 ; lactation in, 554 ; fer-
tility in, 587, 592 ; 671
Rohrig, 528, 577
Rolleston, 458
Rollinat, 186
Rolph, 627
Romanes, 206
Rommel and Phillips, 605
Rorig, 314
Ross, 13 n.
Rossi, Pierre, experiment by, 182
Roth, 180
Rouget, 140, 526
Routh, 538 ,97., 577
Roux, 216
Rubaschkin, 132, 135
Rubinstein, 319
Runge, E., 671
- M., 530
Ruticilla phcenicurus, 316
Rutting season, defined, 35 sq.
S
Sadler, 646
Sagartia troglodytes, 8 sq., 679
Sainmont, 124
Salamander, 23, 177
Salamander maculosa, 186
Salmon, 18 sq., 28, 31, 278 sqq., 288,
292 sq., 295
Salvi, 62
Sanderling, 24
Sandes, 149, 158, 337, 339
Sanger, 365
Sanson, 629
Sanysil, 63
Sarcophytum, 9
Saunders, 194
Sauropsida, 378, 380
Sauve, 320
Savare, 481 sq.
Sawflies, 131 n., 629
Sehafer, 24 sq., 116 sq.. 153, 556, 562,
565, 569
Scharf, 55
Schenk, 630. See also Kleinhaus
and Schenk
Schmidt, Albert, 358, 405, 446
, H., 47
Schmiedeberg, 297, 299
Schmorl, 493
Schneidemiihl, 240
Sehorndorff, 54
Sehottlander, 156 sqq.
Sehrader, 516
Sehreiner, 28 ~>
Schroder, 68
INDEX
703
Schron, 118
Schulin, 156 sq.
Schultz, 320
Sehultza, 393, 642, 647, 650
Schutz, 532
Schweigger-Seidel, 173
Sciurus vulgaris, 41
Sclater, 65
Sclerophytum, 9
Scorpion, 350
Scyllium, 277
Seal, gestation of, 32 ; breeding
season of, 59 sq.
Sea-urchin, 199, 225, 301. See also
under generic names
Sedgwick, 6r 73, 186
Seeliger, 199
Seitz, 149, 156, 158
Selenka, 382, 392, 420, 465
Seligmann, 305, 306. See also
Shattock and Seligmann
Semen, chemistry of, 282 sqq.
Seminal fluid, 176
Semnopithecus entellus, 63, 89 sqq., 97
Semnopithecus nasicus, 464
Semon, 18, 38, 39
Semper, 10, 12, 14, 15, 22, 31
Senescence, 675 sqq.
Seps, 151
Seps chalcides, 380
Serralaeh and Pares, 238
Serres, 528
Sertoli, 253
Seubert, 232
Sex, determination of, chap. xv.
Sfameni, 68
Shad, 18
Sharpey, 400, 466
Shattock and Seligmann, 311, 315
Sheep, 26 ; dicestrous cycle in, 37 ;
cestrous cycle in, 42 sqq., 107 sqq. ;
ovulation in, 136 ; corpus luteum
in, 147 sq., 152 ; 183 ; Mendelian
experiments on, 198 ; in-breeding
in, 209 ; accessory reproductive
organs in, 229, 247 sq. ; castra-
tion in, 306 ; foetal nutrition in,
371, 376, 380, 386, 396 sq., 400,
403 sq., 407, 417, 427, 435, 484,
487 ; pregnancy in, 495, 508,
520 ; parturition in, 535 ; lacta-
tion in, 554 sq. ; fertility in, 590
sq., 596 sqq., 604 ; abortion in,
612 sq., 617 sqq. ; growth of, 668 ;
age attained bv, 681
Sherrington, 255/259, 330
Shortt, 44, 47
Shrew, breeding season of, 60 ;
fcetal nutrition in, 372, 377, !
391 sq., 452-5
Siebold, von, 186, 628 sq.
Sigismund, 162
Silkworm moth, 184, 217, 280 sq.,
307, 626
Simocephalus, 632, 644
Simpson, Sir James, 537, 541
- J. Y., 213
Simpson (Sutherland) and Marshall,
262
Sims, 609
Sinety, 510. S°e also De Sin6ty
Siphostomafloridce, 652
Sipunculids, 224
Sirenia, 376 sq., 553
Sixta, 38 n.
Skin, changes in, during pregnancy,
523
Slemons, 499, 505, 517
Slocum, 524
Sloth, 402, 553
Slowtzoff, 283
Smith, F., 314, 536, 667, 669,
678
- Geoffrey, 308, 640, 653. 658
- Tyler, 542
Smyth, 126
Snail, 186
Snakes, scent-glands of, 31
Snipe, 27
Sobotta, 42, 132, 143 sqq., 150, 156.
233, 439
Sokoloff, 317
Soli, 349
Somerset, 58
Sow, cestrous cycle in, 50, 334 ;
ovulation in, 135 ; 145 ; in-breed-
ing in, 208 ; fcetal nutrition in.
386, 394 sqq., 403, 484; partu-
rition in, 537 ; fertility of, 586,
591, 600, 605, 671
Spallanzani, 4, 19 sq., 22, 23, 56,
140, 165, 181 sqq., 203
Sparrow, 24, 26, 157
Speeht, 607
Spee, von, 363, 393, 443 sqq., 449,
466
Spencer, Herbert, 587 sqq.
Spermatogenesis, chap. v.
Spermatozoa, structure of, 172 sqq. ;
movements of, 176 sqq. ; chemo-
tactic properties of, 214 sqq. ;
chemistry of, 288 sqq.
Spermophilus, 150
Sphoerechinus, 179, 300
Sphcer echinus granulosus, 293, 300
Spider crab, 307
Spiegelberg, 542 sq.
Spiegelberg and Gscheidlen, 520 sq.
Spina, 254
Spinax, 151
704
INDEX
Spitzer, 299
Sorex, 144, 150
Stag, breeding season of, 27 sg. ;
effects of castration on, 305
Starfish. See Asterias
Starkweather, 647
Starling, 26
Starling, 335, 352, 492. See also
Lane-Claypon and Starling
Steinach, 234, 236 sq.
Steinhaus, 89, 560 sq.
Stenops, 250
Sterility, 606 sqq.
Steudei; 294, 295, 296
Stevens, 12, 631, 633
Stevenson, 67 sq. See also News-
holme and Stevenson
Stilling, 232, 240, 350
Stoat, breeding season of, 59
Stockel, 146
Stolz, 512
Stonehenge, 53 sq.
Strahl, 361, 364, 376, 403, 410,
413 sq., 416, 456, 458, 551 sq.
Strasburger, 187, 215
Strassmann, 85, 185, 329
Stratz, 61, 62, 97, 113
Stricht, van der, 122, 132, 137, 148,
150, 156, 460
Strongylocentrotus, 204 sq.
Strongylocentrotus lividus, 300
Strongylocentrotus purpuratus, 219
Sturgeon, 18
Stychostemma asensoriatum, 10
Stylonychia, 212
Stylonychia pustulata, 6
Suehet'et, 604
Superf rotation, 159 sqq.
Sutton, 130
- Bland, 89, 95, 97, 343
Swan, 26
Swayne, 49
Swifts, 25
Symplasma, defined, 414
Szabo, 561
T
Tadpole, 624 sq.
Tafani, 135, 403
Tait, 163, 522
Talpa, 250
Tandler and Gross, 306
Tangl, 272, 434
Tangl and Farkas, 273, 302
Tapir, 247
Tarchanoff, 22, 234, 275
Tarsius, 144, 150 ; foetal nutrition
in, 408, 410, 463, 494 ; 552
Tarsius spectrum, 62, 97 sq., 137,
551 n.
Tchermak, 193
Teacher, 138. See also Bryce and
Teacher
Tegetmeier and Sutherland, 584
Telegony, 201 sq.
Teleoste, 16, 151, 277
Tennent, 226
Tenrec, 458
Tergipes, 15
Termite, 627
Terrier, 516
Tessier, 545
Testis, influence of, 303 sqq. ; in
Man, ib. ; stag, 305 ; fallow deer,
ib. ; sheep, 306 ; horse, 307, 310 ;
arthropods, 307 ; fowl, 311 sq. ;
frog, 312 sqq. ; relation between
thymus and, 349 ; 353
Thiemich, 495, 512
Thierfelder, 569, 572
Thierf elder and Stern, 267
Thompson, 289
Thomson, J. A., 165, 201, 623,
648. See also Geddes and Thomson
- H., 507
Thudichum, 264, 267
Thury, 630
Thymus, relation between testis
and, 349
Tichomiroff, 217, 280 sq.
Tiedemann, 241
Tiger, 247
Timofeew, 258
Toad, breeding season in, 20 ;
ovulation in, 140 ; 300
Torelle, 216
Tortoise, 22, 31, 278, 680
Treadwell, 224
Treat, 625
Trematode, 10
Treviranus, 192
Triton, 174
Triton alpestris, 202 sq.
Triton waltlii, 22
Tropidonotus, 277
Tropidonotus viperinus, 186
Truzzi, 523
Tupaia, 144, 150, 250, 377, 457 sq.,
494, 552 n.
Tupaia javanica, 61, 98 sq., 372,
392, 457 sq.
Turbot, 205
Turner, 60, 359, 361, 369, 376, 388,
395, 401, 408, 410, 463
Twins, pygopagous, 585
U
Ulesco-Stroganowa, 479
Ungulata, oestrous cycle in, 42 ;
INDEX
705
foetal nutrition in, 375, 386,
394 sqq., 417 sq., 484 ; lactation
in, 553 sq. ; fertility in, 586
Uterus, structure of, 75 sqq. ;
changes in, during cestrous cycle,
chap. iii. ; significance of pro-
oestrous changes in, 161 sqq. ;
supposed internal secretion of,
345 sqq. ; innervation of, 527 sqq.
Surnames with van and von are in-
dexed under name following.
Valenciennes and Fremy, 278
Valentin, 114, 252
Vallet, 526
Vaughan, 264
Veit, 493 sq., 506, 523, 587
Veit and Seholten, 480, 493, 515
Ver Eeke, 498, 500 sq., 503, 516
Vernhout, 456
Vernon, 203 sq.
Verworn, 178 sq., 197, 200, 299,
570, 659, 683
Vesiculas seminales, 231 sqq.
Vesperugo, 148, 150, 156
Vesperugo noctula, 132
Vespertilia, 148
Vicarelli, 68. See also Oddi and
Vicarelli
Virchow, 559, 570
Voit, 510
Volker, 149
W
Wade and Watson (B. P.), 369, 474
Waldeyer, 114 sqq., 143, 184, 271,
358 sq.
Walker, C. E., 312
Walker, G., 237, 239, 309 sq.
Wallace, A. R., 27, 603
- Cuthbert, 239, 303
— R., 17 ; oestrous cycle, 45, 47,
50, 51; 151, 214, 248, 307, 495;
lactation, 566 sqq. ; fertility,
596, 599, 600, 604, 608; 616;
654
Wallart, 354
Walrus, breeding season of, 49, 60 ;
246
Walther, 278
Wapiti deer, oestrous cycle in, 49;
305 n.
Water-buck, cestrous cycle in, 49
Watson, M., 250
- B. P., 565. See also Paton,
Kerr, and Watson
- Chalmers, 595
Weasel, breeding season of, 59
Webb, Sidney, 621 sq.
Weber, 313, 358 sqq., 375
Webster, 80, 138, 164, 367, 474,
476 sq.
Weichardt and Opitz, 493
Weil, 135
Weininger, 654 sqq.
Weinland, 302
Weismann, 172, 191, 192 sqq., 628,
631, 679 sq., 682 sq.
Weiss, 292
" Wellenbewegung " hypothesis, 67,
164
Wendeler, 118, 145
Westermarek, 70 sq.
Westphalen, 82 sq., 85, 87, 89
Werth, 369
Whales, breeding period of, 52 sq. ;
age of, 680
Wheeler, 629
Whetham, 622
Whitney, 7
Widal, 517
Widgeon, 315
Wiedersheim, 554 sq.
Wiener, 365
Wild, 520
Willcock and Hardy, 275
Willey, 16
Williams, Whitridge, uterus, 85,
88 ; 149, 180, 336 ; female genera-
tive organs, 532 sq., 540 sq.,
543 sq., 548 sq., 551; 565 sqq.,
587, 632
- Sir J., 83, 549
Wilson, E. B., changes in the ovary,
113, 122, 130, 131 ; spermato-
genesis, 172, 174, 175 ; 190, 216,
226, 356 ; sex-determination, 633,
636
S. M., 48
Wiltshire, 19, 25, 39, 50, 62, 66
Winckel, 505, 517, 522
Winckelmann, 520
Wini water, van, 117s?., 131
Winkler, H., 300
- F. N., 360
Winterhalter, 329
Winterstein and Stickler, 524
Win wood Reade, 63
Wohlgemuth, 276
Wolf, breeding season of, 55
Wolfe, 513
Wood, 198
Woodruff, 214
Worthmann, 250
Wright, 23, 316
Wychgel, 516, 523
Wyder, 88
2Y
70(j
INDEX
x
Xenia hicksoni, 9
Xenopus la vis, 20 sqq.
Y
Yak, 49
Yolk-sac, 378 ; nutritive
ance of, 380 sqq.
Yule, 621
Youatt, 334
Yung, 625
Zaeharjewsky, 497 sq., 503, 505 sq.,
510
Ziegler, 641
Zoarces, 151
import- i Zoth, 309
Zuntz, L., 68, 355
- E., 519
Zweifel, 505
Zweifel and Abel, 346
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